[go: up one dir, main page]
More Web Proxy on the site http://driver.im/

CN117257782B - Application of melitracin in reversing Oritinib resistance - Google Patents

Application of melitracin in reversing Oritinib resistance Download PDF

Info

Publication number
CN117257782B
CN117257782B CN202311478635.8A CN202311478635A CN117257782B CN 117257782 B CN117257782 B CN 117257782B CN 202311478635 A CN202311478635 A CN 202311478635A CN 117257782 B CN117257782 B CN 117257782B
Authority
CN
China
Prior art keywords
lung cancer
melitracin
octreotide
cells
small cell
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN202311478635.8A
Other languages
Chinese (zh)
Other versions
CN117257782A (en
Inventor
雷雪萍
余细勇
陈卓文
邓秋狄
孙海燕
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Guangzhou Medical University
Original Assignee
Guangzhou Medical University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Guangzhou Medical University filed Critical Guangzhou Medical University
Priority to CN202311478635.8A priority Critical patent/CN117257782B/en
Publication of CN117257782A publication Critical patent/CN117257782A/en
Application granted granted Critical
Publication of CN117257782B publication Critical patent/CN117257782B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Landscapes

  • Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention discloses an application of melitracin in reversing the drug resistance of octreotide. The invention discovers that the meritroxine or the meritroxine combined with the octreotide can inhibit the proliferation and the clonogenic capacity of lung cancer cells for the first time and can improve the intracellular ROS level of the lung cancer cells. The meretridine and the octreotide have synergistic effect, can obviously enhance the apoptosis capability of the octreotide on PC9/OR cells, and obviously improve the intracellular ROS level of lung cancer cells so as to further promote the apoptosis of the lung cancer cells and enhance the treatment effect of the lung cancer cells (especially non-small cell lung cancer). The invention discovers that the melitracin has a reversing effect on the acquired resistance of the lung cancer of the octreotide for the first time, provides a new method and a new strategy for overcoming the resistance of the octreotide, and simultaneously provides a new application of the melitracin.

Description

Application of melitracin in reversing Oritinib resistance
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to an application of melitracen in reversing the drug resistance of octreotide.
Background
Lung cancer is a malignant tumor with high morbidity and mortality worldwide. Of these, about 80-85% are Non-small cell lung cancer (NSCLC). In recent years, molecular targeted drugs such as EGFR tyrosine kinase inhibitors (EPIDERMAL GROWTH FACTOR RECEPTOR-tyrosine kinase inhibitor, EGFR-TKI) have made a breakthrough in the clinical treatment of NSCLC.
Ornitinib (Osimertinib, osi) is the first third generation EGFR-TKI approved by the FDA in the United states, and can selectively irreversibly bind to sensitive mutant EGFR and T790M resistant mutant EGFR to block downstream signaling so as to achieve the purpose of resisting tumors. In view of its good clinical efficacy and safety, the drug is recommended for first-line treatment of EGFR mutation positive NSCLC patients.
However, also of octenib there is acquired resistance, leading to failure of treatment, disease progression. The reasons for acquired drug resistance are very complex, and the molecular mechanisms that have been found at present mainly comprise two main classes: EGFR-dependent mechanisms, such as EGFRC797S mutations, etc.; EGFR independent mechanisms such as compensatory signaling pathway establishment of c-MET, HER2 and the like, pathological tissue type transformation and the like. In order to overcome the drug resistance of the Ornitinib and enhance the curative effect of the Ornitinib, the present researches show that the panobinostat, the aspirin and the curcumin have a certain reversal effect on the acquired drug resistance of the EGFR-TKI drugs of NSCLC cells, but the drug reversal agent with higher safety, stable curative effect and better effectiveness still needs to be further explored and discovered.
Disclosure of Invention
Based on this, the present invention aims to provide a reversing drug having a reversing effect on the acquired resistance of the lung cancer of octenib.
In order to achieve the above object, the present invention includes the following technical solutions.
In a first aspect, the present invention provides the use of melitracin in the manufacture of a medicament for the prevention and/or treatment of lung cancer.
In some of these embodiments, the lung cancer is an octenib acquired resistant lung cancer.
In some of these embodiments, the lung cancer is human non-small cell lung cancer.
In a second aspect, the invention provides the use of melitracen in combination with octreotide for the manufacture of a medicament for the prevention and/or treatment of lung cancer.
In some of these embodiments, the lung cancer is an octenib acquired resistant lung cancer.
In some of these embodiments, the lung cancer is human non-small cell lung cancer.
In a third aspect, the present invention also provides a combination for the prevention and/or treatment of lung cancer, the active ingredients of which include melitracin and octreotide, which are separate administration units, or which together form a combined administration unit.
In some of these embodiments, the molar ratio of melitracin to octreotide is from 0.5 to 5:1.
In some of these embodiments, the molar ratio of melitracin to octreotide is from 1 to 3:1.
In some of these embodiments, the molar ratio of melitracin to octreotide is from 1.5 to 2.5:1.
In some of these embodiments, the molar ratio of melitracin to octreotide is from 1.8 to 2.2:1.
In some of these embodiments, the molar ratio of melitracin to octreotide is 2:1.
In some of these embodiments, the lung cancer is an octenib acquired resistant lung cancer.
In some of these embodiments, the lung cancer is human non-small cell lung cancer.
In a fourth aspect, the invention also provides the use of melitracin in the manufacture of a reversal medicament for reversing acquired resistance of octreotide in lung cancer.
In some of these embodiments, the lung cancer is human non-small cell lung cancer.
In a fifth aspect, the invention also provides a method for reversing the acquired resistance of the octreotide for lung cancer, which adopts the combination of a reversing drug and the octreotide to realize the reversing of the acquired resistance of the octreotide for lung cancer; the reversing drug is melitracin.
Wherein the melitracin and the octreotide are separate administration units, respectively, or the melitracin and the octreotide together form a combined administration unit, i.e., the melitracin and the octreotide may be administered simultaneously or separately.
In some of these embodiments, the molar ratio of melitracin to octreotide is from 0.5 to 5:1.
In some of these embodiments, the molar ratio of melitracin to octreotide is from 1 to 3:1.
In some of these embodiments, the molar ratio of melitracin to octreotide is from 1.5 to 2.5:1.
In some of these embodiments, the molar ratio of melitracin to octreotide is from 1.8 to 2.8:1.
In some of these embodiments, the molar ratio of melitracin to octreotide is 2:1.
In some of these embodiments, the lung cancer is human non-small cell lung cancer.
The invention discovers that the meretridine or the meretridine combined with the octreotide can inhibit the proliferation and the clone formation of lung cancer cells and simultaneously improve the intracellular ROS level of the lung cancer cells for the first time. The meretridine and the octreotide have synergistic effect, can obviously enhance the apoptosis capability of the octreotide on PC9/OR cells, and obviously improve the intracellular ROS level of lung cancer cells so as to further promote the apoptosis of the lung cancer cells and enhance the treatment effect of the lung cancer cells (especially non-small cell lung cancer).
The invention discovers that the melitracin has a reversing effect on the acquired resistance of the lung cancer of the Ornitanib for the first time, provides a new method and a new strategy for overcoming the resistance of the Ornitanib, and simultaneously provides a new application of the melitracin in preparing a medicine for preventing and/or treating the lung cancer or preparing a medicine for reversing the acquired resistance of the lung cancer of the Ornitanib.
Drawings
FIG. 1 is a validation result of NSCLC octenib acquired drug resistant cell model; wherein,
A is the octenib IC50 value of the parent cells and the drug resistant cells detected by the CCK8 experiment;
b is q-PCR experiment to detect the gene expression condition of ABCB 1;
c is the protein expression condition of the ABCB1 detected by a WB experiment.
FIG. 2 is the effect of melitracin on PC9/OR cell viability; wherein,
A is the structural formula of melitracin;
b is the IC50 value of the melitracin detected by CCK8 experiment;
c is a clone formation experiment to detect the clone inhibition ability of the melitracin on drug-resistant cells.
FIG. 3 is the effect of a combination of melitracin and octreotide on PC9/OR cells; wherein,
A is the result of flow cytometry detection of apoptosis;
b is the result of flow cytometry detection of cellular ROS levels.
Detailed Description
The technical scheme of the invention is further described by the following specific examples. It will be apparent to those skilled in the art that the examples are merely to aid in understanding the invention and are not to be construed as a specific limitation thereof.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention.
The terms "comprising" and "having" and any variations thereof, are intended to cover a non-exclusive inclusion. For example, a process, method, apparatus, article, or device that comprises a list of steps is not limited to the elements or modules listed but may alternatively include additional steps not listed or inherent to such process, method, article, or device.
In the present invention, the term "plurality" means two or more. "and/or", describes an association relationship of an association object, and indicates that there may be three relationships, for example, a and/or B, and may indicate: a exists alone, A and B exist together, and B exists alone. The character "/" generally indicates that the context-dependent object is an "or" relationship.
In order to overcome the drug resistance of the octreotide and enhance the curative effect of the octreotide, the invention discovers a reversing agent (reversing drug) for the acquired drug resistance of the octreotide through a great deal of research and exploration; the research result of the invention shows that: the nervous system medicine-melitracin, a tricyclic diphase antidepressant with oral activity, can obviously enhance the anti-tumor capability of the octreotide and has good anti-tumor effect combined with the octreotide.
In one embodiment of the present invention, the present invention provides the use of melitracen in the manufacture of a medicament for the prevention and/or treatment of lung cancer.
The lung cancer can be common lung cancer or lung cancer with acquired resistance to the drug of the Ornitinib.
Further preferably, the lung cancer is human non-small cell lung cancer.
In another embodiment of the invention, the invention provides the use of melitracen in combination with octreotide for the manufacture of a medicament for the prevention and/or treatment of lung cancer.
The lung cancer can be common lung cancer or lung cancer with acquired resistance to the drug of the Ornitinib.
Further preferably, the lung cancer is human non-small cell lung cancer.
In another embodiment of the present invention, the present invention also provides a combination for preventing and/or treating lung cancer, the active ingredients of which include melitracin and octreotide, which are separate administration units, or which together form a combined administration unit. I.e. the melitracin and the octreotide may be administered simultaneously or separately, the molar ratio of melitracin to octreotide being between 0.5 and 5:1, preferably 1-3:1, further preferably 1.5 to 2.5:1, further preferably 1.8 to 2.2:1, more preferably 2:1.
The lung cancer can be common lung cancer or lung cancer with acquired resistance to the drug of the Ornitinib.
Further preferably, the lung cancer is human non-small cell lung cancer.
The combined medicine of the invention can also be prepared into a pharmaceutical preparation for preventing and/or treating tumors with pharmaceutically acceptable auxiliary materials. The pharmaceutical formulations may be administered to a patient in a variety of routes of administration including, but not limited to, oral, transdermal, intramuscular, subcutaneous, and intravenous injection.
The dosage form of the combined drug of the invention is not limited, and the combined drug can ensure that the active ingredients can reach the dosage form in vivo effectively, and comprises the following components: injection, tablet, film coated tablet, enteric coated tablet, capsule, buccal preparation, granule, powder, unguent, pellet, suspension, pill, powder, spray, drop, suppository, cream, patch, etc.; injection forms are preferred, such as: liquid injection, powder injection, injection tablet, etc.; injection forms include, but are not limited to, crude drug forms, drug-loaded nanoparticles, and the like; injection sites include, but are not limited to, intradermal injection, subcutaneous injection, intramuscular injection, intravenous injection, spinal cavity injection, and the like.
In another embodiment of the invention, the invention also provides the use of melitracin in the manufacture of a reversal medicament for reversing acquired resistance of octreotide in lung cancer.
Wherein the lung cancer is preferably human non-small cell lung cancer.
In another embodiment of the invention, the invention also provides a method for reversing the acquired resistance of the lung cancer of the octenib, which adopts the combination of the reversing drug and the octenib to realize the reversing of the acquired resistance of the lung cancer of the octenib; the reversing drug is melitracin.
Wherein the melitracin and the octreotide are separate administration units, respectively, or the melitracin and the octreotide together form a combined administration unit, i.e., the melitracin and the octreotide may be administered simultaneously or separately. When the medicine is administrated, the molar ratio of the melitracin to the octreotide is 0.5-5:1, preferably 1-3:1, further preferably 1.5 to 2.5:1, further preferably 1.8 to 2.2:1, more preferably 2:1.
Wherein the lung cancer is preferably human non-small cell lung cancer.
The invention induces an octreotide drug-resistant cell model by a drug large-dose impact method, utilizes CCK-8 to detect IC50 values of the octreotide in different cells, calculates a drug-resistant coefficient, detects the expression level of a multi-drug-resistant gene ABCB1 by a real-time fluorescent quantitative polymerase chain reaction (Quantitative polymerase chain reaction, qPCR) experiment and a western blotting experiment (WB), and verifies whether the octreotide drug-resistant cell model is successfully constructed. On this basis, the antitumor effect of melitracin and the combination of melitracin and octreotide was evaluated by CCK-8, flow cytometry and cell clone formation experiments, and the synergy was determined by CI values. Meanwhile, the RNA-seq is used for detecting the differential change in drug-resistant strains after the combined drug and the single drug. The invention is proved by the scientific experiments that: the meretridine combined with the octreotide can remarkably inhibit the proliferation capability of an octreotide acquired drug resistant cell model PC9/OR induced by human lung adenocarcinoma PC9 cells, and simultaneously raise the level of active oxygen (reactive oxygen species, ROS) of the cells and promote apoptosis.
The following materials were used in the examples:
RPMI1640 medium, penicillin-streptomycin (100X) was purchased from Gibco corporation, USA;
fetal bovine serum was purchased from the biosciences company of escitalopram, china;
ornitinib (T2490), melitracin (T4274) was purchased from Shanghai Tao Shu Biotechnology Co., ltd;
H2DCFDA (HY-D0940) was purchased from MCE company, USA;
CCK-8 kit (FD 3788) was purchased from Friedel biotechnology Co., ltd;
apoptosis assay kit (KGA 105) was purchased from Jiangsu Kaiki Biotechnology Co., ltd.
The following are specific examples.
Example 1 establishment and verification of NSCLC Ornitinib acquired drug resistant cell model
1. Cell culture
Human non-small cell lung cancer cell line PC9 (EGFR gene exon 19 deletion mutation) was purchased from basic medical institute of China medical sciences. PC9 cells were cultured in RPMI1640 medium containing 10% fetal bovine serum, 1% penicillin and streptomycin, and cultured in a 5% CO 2 incubator at 37 ℃.
2. Drug resistance model establishment
And establishing an Aoditinib-derived drug-resistant cell strain PC9/OR by using the Aoditinib-sensitive PC9 cells according to a drug large-dose impact method. PC9 cells in the logarithmic phase were treated with octenib at a concentration of 10. Mu.M for 48h, and after withdrawal, the cells recovered to growth to about 80% of the growth density, which was one shock cycle, and subjected to multiple drug shock cycles until the cells could stably grow in the 2. Mu.M octenib-containing medium, i.e., PC9/OR cells were successfully induced.
3. Drug resistance model verification
(1) Cell viability was detected using the CCK-8 assay. The method comprises the following steps:
Taking PC9 and PC9/OR cells in logarithmic growth phase, inoculating the PC9 and PC9/OR cells into a 96-well plate (3X 10 3 cells/well), culturing for 24 hours, adding different concentrations of the Ornitinib after the cells are attached, treating for 48 hours at 37 ℃ under the condition of 5% CO 2, adding 10% of CCK-8 detection reagent, continuously incubating for 1 hour, detecting the absorbance at 450nm by using an enzyme-labeling instrument, and calculating the half-maximal inhibitory concentration (halfmaximal inhibitory concentration, IC 50) of the cells; cell viability (%) = (experimental group absorbance-blank group absorbance)/(control group absorbance-blank group absorbance).
The results are shown as a in fig. 1: the IC50 values of octenib in PC9 and PC9/OR were 0.193. Mu.M and 9.493. Mu.M, respectively.
(2) The expression change of the multidrug resistance gene ABCB1 in the cells is detected by adopting a real-time fluorescence quantitative polymerase chain reaction (Quantitativepolymerase chain reaction, qPCR) and a western blotting experiment (Westernblotting, WB). The method comprises the following steps:
PC9 and PC9/OR cells in logarithmic growth phase were inoculated into 6-well plates (2X 10 5 cells/well), and after 48 hours of culture at 37℃under 5% CO 2, cellular RNA and total protein were extracted and qPCR and WB experiments were performed, respectively.
The results are shown in FIG. 1 as B (q-PCR assay to detect gene expression of ABCB 1) and C (WB assay to detect protein expression of ABCB 1): ABCB1 expression is elevated in PC9/OR cells.
The above results indicate that: the obtained drug resistant cell strain PC9/OR of the Ornitinib is successfully established and obtained.
Example 2 effect of melitracin on PC9/OR cell viability
Melitracin (MELITRACEN) is an orally active tricyclic biphasic antidepressant of the formula shown as a in figure 2. Melitracin inhibits the absorption of norepinephrine (Norepinephrine) and 5-hydroxytryptamine (5-HT) through the presynaptic membrane, thereby increasing the concentration of single amine transmitters in the synaptic cleft, and is useful for the treatment of depression and anxiety.
1. The effect of melitracin on PC9/OR cell viability was examined using the CCK-8 method. The method comprises the following steps:
Taking PC9/OR cells in logarithmic growth phase, inoculating the PC9/OR cells into a 96-well plate (3X 10 3 cells/well), culturing for 24 hours, adding different concentrations of meli Qu Xinyu ℃ under the conditions of 5% CO 2 after the cells are attached, treating for 24 hours and 48 hours, adding 10% CCK-8 solution for continuous incubation for 1 hour, and calculating half-inhibition concentration (halfmaximal inhibitory concentration, IC 50) of the cells after detecting the absorbance at 450nm by an enzyme-labeling instrument; cell viability (%) = (experimental group absorbance-blank group absorbance)/(control group absorbance-blank group absorbance).
The results are shown in fig. 2B: IC50 values for PC9/OR cells treated with melitracin for 24h and 48h were 26.72. Mu.M and 17.85. Mu.M, respectively.
2. The effect of melitracin on PC9/OR cell viability was examined using a plate clone formation assay.
The method comprises the following steps:
taking PC9/OR cells in logarithmic growth phase, inoculating into 6-well plate (1×10 3 cells/well), culturing for 24 hr, adding melitracin with different concentrations after the cells are adhered, treating at 37deg.C under 5% CO 2 for 48 hr, changing into culture medium without medicine, and culturing for 7 days. Cells were fixed with 4% paraformaldehyde and then stained with crystal violet.
The results are shown as C in fig. 2: after treatment of PC9/OR cells with melitracin for 48h, the clonogenic potential of the cells was significantly inhibited.
Example 3 effects of combination of melitracin and Ornitinib on PC9/OR cells
1. Apoptosis was detected using flow cytometry. The method comprises the following steps:
The PC9/OR cells in logarithmic growth phase were inoculated into 6-well plates (2X 10 5 cells/well), cultured for 24 hours, treated with 10. Mu.M melitracin, 5. Mu.M octreotide, and combination drug (10. Mu.M melitracin, 5. Mu.M octreotide) after cell attachment, and all cells were collected after 24 hours treatment at 37℃under 5% CO 2. And washing, fixing and staining the cells according to a commercial apoptosis kit, and finally recording fluorescence intensities of an excitation wave FITC channel and a PE channel by using a flow cytometer to analyze apoptosis conditions.
The results are shown in fig. 3 a: the combination regimen significantly enhanced the apoptosis capacity of the oritinib on PC9/OR cells.
2. The ROS levels of the cells were detected using flow cytometry. The method comprises the following steps:
The PC9/OR cells in logarithmic growth phase are inoculated in a 12-well plate (1X 10 5 cells/well), cultured for 24 hours, 10 mu M of meritrecine, 5 mu M of Orientinib and combined medicines (10 mu M of meritrecine and 5 mu M of Orientinib) are added to treat the cells, the original culture medium is discarded after 24 hours of treatment at 37 ℃ and 5% CO 2, 10 mu M of DCFH-DA-containing culture medium (500 mu L/well) is added to dye for 30 minutes at 37 ℃ in a dark place, PBS (500 mu L/well) is used for washing the cells twice, so that DCFH-DA which does not enter the cells is sufficiently removed, and the cells are collected for flow cytometry, the fluorescence intensity of FITC channels is detected, and the ROS level in the cells is analyzed.
The results are shown in fig. 3B: the combined regimen significantly increased ROS levels in PC9/OR cells.
The technical features of the above-described embodiments may be arbitrarily combined, and all possible combinations of the technical features in the above-described embodiments are not described for brevity of description, however, as long as there is no contradiction between the combinations of the technical features, they should be considered as the scope of the description.
The above examples illustrate only a few embodiments of the invention, which are described in detail and are not to be construed as limiting the scope of the invention. It should be noted that it will be apparent to those skilled in the art that several variations and modifications can be made without departing from the spirit of the invention, which are all within the scope of the invention. Accordingly, the scope of protection of the present invention is to be determined by the appended claims.

Claims (8)

1. Use of melitracin in the manufacture of a medicament for the prevention and/or treatment of non-small cell lung cancer in humans.
2. Use of melitracin in combination with octreotide in the manufacture of a medicament for the prevention and/or treatment of non-small cell lung cancer in humans.
3. The use according to claim 1 or 2, wherein the human non-small cell lung cancer is an octenib acquired drug resistant human non-small cell lung cancer.
4. A medicament for preventing and/or treating non-small cell lung cancer in a human, characterized in that the active ingredients thereof comprise melitracin and octtinib, which are separate administration units, respectively, or which together form a combined administration unit.
5. The drug for preventing and/or treating human non-small cell lung cancer according to claim 4, wherein the molar ratio of melitracen to octenib is 1-3:1.
6. The medicament for preventing and/or treating non-small cell lung cancer in humans according to claim 5, wherein the molar ratio of melitracen to octenib is 1.5-2.5:1.
7. The medicament for preventing and/or treating non-small cell lung cancer in humans according to claim 6, wherein the molar ratio of melitracen to octenib is 1.8-2.2:1.
8. Use of melitracin in the manufacture of a reversal drug for reversing the acquired resistance of octenib in human non-small cell lung cancer.
CN202311478635.8A 2023-11-07 2023-11-07 Application of melitracin in reversing Oritinib resistance Active CN117257782B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202311478635.8A CN117257782B (en) 2023-11-07 2023-11-07 Application of melitracin in reversing Oritinib resistance

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202311478635.8A CN117257782B (en) 2023-11-07 2023-11-07 Application of melitracin in reversing Oritinib resistance

Publications (2)

Publication Number Publication Date
CN117257782A CN117257782A (en) 2023-12-22
CN117257782B true CN117257782B (en) 2024-08-30

Family

ID=89210720

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202311478635.8A Active CN117257782B (en) 2023-11-07 2023-11-07 Application of melitracin in reversing Oritinib resistance

Country Status (1)

Country Link
CN (1) CN117257782B (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN118161493B (en) * 2024-05-14 2024-08-09 南昌大学第一附属医院 Application of entinostat in preparation of drug for treating drug-resistant non-small cell lung cancer

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108362792A (en) * 2018-01-31 2018-08-03 成都倍特药业有限公司 A kind of detection method of flupentixol and melitracen compound medicine impurity, new recognizable impurity and safer compound medicine
CN116173164A (en) * 2023-04-06 2023-05-30 曾碧文 Traditional Chinese medicine composition for treating liver cancer and postoperative radiotherapy and chemotherapy and preparation method thereof

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014018563A2 (en) * 2012-07-23 2014-01-30 The Board Of Trustees Of The Leland Stanford Junior University Methods for the treatment of cancer
KR102312100B1 (en) * 2020-06-05 2021-10-14 (주)프론트바이오 Pharmaceutical composition for preventing or treating cancer comprising antivirals, and antidepressants thereof as active ingredients

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108362792A (en) * 2018-01-31 2018-08-03 成都倍特药业有限公司 A kind of detection method of flupentixol and melitracen compound medicine impurity, new recognizable impurity and safer compound medicine
CN116173164A (en) * 2023-04-06 2023-05-30 曾碧文 Traditional Chinese medicine composition for treating liver cancer and postoperative radiotherapy and chemotherapy and preparation method thereof

Also Published As

Publication number Publication date
CN117257782A (en) 2023-12-22

Similar Documents

Publication Publication Date Title
EP3838333B1 (en) Using alternating electric fields to increase cell membrane permeability
Liu et al. A potential target associated with both cancer and cancer stem cells: a combination therapy for eradication of breast cancer using vinorelbine stealthy liposomes plus parthenolide stealthy liposomes
CN104083365A (en) Cancer treatment
CN101888777A (en) Treatment of cancer with combinations of topoisomerase inhibitors and PARP inhibitors
CN105338973A (en) Treatment of cancer using coenzyme q10 combination therapies
KR20100016385A (en) Method of treating brain cancer
CN117257782B (en) Application of melitracin in reversing Oritinib resistance
CN111358952B (en) Anti-tumor pharmaceutical composition, preparation and application thereof
CN104800858B (en) HSP90 suppresses peptide conjugate and its application in oncotherapy
CN109464460A (en) A kind of pharmaceutical composition and its application in preparation of anti-tumor drugs improving anti-tumor drug sensibility
CN116808176B (en) Anti-tumor pharmaceutical composition based on immune checkpoint blocking and application thereof
CN114948947B (en) Application of fenticonazole nitrate in preparing antitumor drug
CN110314222A (en) Application of the composition of bortezomib and pabishta or Vorinostat in the drug of preparation treatment drug-resistant type MLL leukaemia
CN106075454A (en) A kind of anti-tumor medicinal preparation combination
CN117427068A (en) Use of a Ji Ruige in the treatment of oritinib-resistant lung adenocarcinoma
CN105251023A (en) Application of AXL/c-Met inhibitor in preparation of drug for reversing renal cancer sunitinib drug resistance
CN110354121A (en) Application of the Ciclopirox Olamine in preparation tumor and composition of medicine and purposes comprising Ciclopirox Olamine
CN110063988A (en) A kind of pharmaceutical composition and preparation method thereof for treating neuroblastoma
CN110403924A (en) A kind of pharmaceutical composition and preparation method thereof for treating cutaneous melanoma
Zhang et al. Molecular-targeted therapy of pancreatic carcinoma and its progress
CN108743591A (en) Pharmaceutical composition for treating cancer and its application
KR102658209B1 (en) Pharmaceutical composition for preventing or treating bladder cancer comprising a CDK inhibitor and an ID2 activator
CN110420328B (en) Application of SYT14 inhibitor in preparation of medicine for treating lung cancer
US20200215150A1 (en) Medicine for combined use in cancer treatment
CN108853114A (en) Application in the drug of nifurtimox metastatic encephaloma derived from preparation treating cancer

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant