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Chimeric antibody targeting SRPK-1 in the treatment of non-small cell lung cancer by inhibiting growth, migration and invasion

Mol Med Rep. 2017 Aug;16(2):2121-2127. doi: 10.3892/mmr.2017.6833. Epub 2017 Jun 21.

Abstract

Non-small cell lung cancer (NSCLC) is one of the most common types of cancer in humans, and is characterized by rapid growth, migration, invasion and reoccurrence. Evidence has indicated that the protein and mRNA levels of serine‑arginine protein kinase‑1 (SRPK‑1) are upregulated in NSCLC tissues. However, the functions of SRPK1 and targeted therapy for SRPK1 in the progression and treatment of NSCLC remain to be fully elucidated. In the present study, the mRNA and protein expression levels of SRPK‑1 in NSCLC cells and tissues were analyzed using reverse transcription‑quantitative polymerase chain reaction analysis and SDS‑PAGE, and the role of SRPK1 in the progression of NSCLC was investigated. In addition, a chimeric antibody target for SRPK‑1 (ChanSRPK‑1) was constructed, and the therapeutic effects of ChanSRPK‑1 were investigated in H358‑bearing mice. The curative effects of ChanSRPK‑1 on the inhibition of growth, migration and invasion of NSCLC were also examined in vitro and in vivo. The results revealed that the mRNA and protein levels of SRPK‑1 were upregulated in NSCLC cells and tumor tissues. Higher expression of SRPK1 promoted NSCLC cell growth, migration and invasion, whereas lower expression of SRPK‑1 suppressed growth, migration and invasion of the NSCLC cells. Animal experiments demonstrated that ChanSRPK‑1 inhibited the β‑catenin/T‑cell factor complex. ChanSRPK‑1 treatment also downregulated the phosphorylation levels of glycogen synthase kinase 3-β and prolonged the survival of tumor‑bearing mice. Taken together, SRPK‑1 may offer potential as a therapeutic target oncogenic molecular in NSCLC, and ChanSRPK‑1 may be a therapeutic agent with functions as a target and for oncolytic therapy in the treatment of NSCLC.

MeSH terms

  • Animals
  • Antibodies / immunology
  • Antibodies / pharmacology*
  • Antibodies / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Down-Regulation / drug effects
  • Glycogen Synthase Kinase 3 beta / metabolism*
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Phosphorylation / drug effects
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / immunology
  • Protein Serine-Threonine Kinases / metabolism*
  • Transplantation, Heterologous

Substances

  • Antibodies
  • SRPK1 protein, human
  • Glycogen Synthase Kinase 3 beta
  • Protein Serine-Threonine Kinases