Inhibition of B7-H3 reverses oxaliplatin resistance in human colorectal cancer cells

Biochem Biophys Res Commun. 2017 Aug 26;490(3):1132-1138. doi: 10.1016/j.bbrc.2017.07.001. Epub 2017 Jul 1.

Authors

Pengfei Zhang¹, Zhen Chen², Kuan Ning¹, Jian Jin³, Xiaofeng Han⁴

Affiliations

¹ Wuxi Medical School, Jiangnan University, Wuxi, Jiangsu, China.
² School of Pharmaceutical Sciences, Jiangnan University, Wuxi, Jiangsu, China.
³ School of Pharmaceutical Sciences, Jiangnan University, Wuxi, Jiangsu, China. Electronic address: jinjian31@126.com.
⁴ Wuxi Medical School, Jiangnan University, Wuxi, Jiangsu, China. Electronic address: xfenghan@126.com.

PMID: 28676400
DOI: 10.1016/j.bbrc.2017.07.001

Abstract

B7-H3, an immunoregulatory protein, has been found highly expressed in several cancer types, and involved in cancer cell migration and invasion. Here, we investigated the role of B7-H3 in oxaliplatin resistance in colorectal cancer (CRC) cells. Transient silencing of B7-H3 enhanced oxaliplatin sensitivity by increasing oxaliplatin-induced DNA damage. The overexpression of B7-H3 increased oxaliplatin resistance reducing the formation of phosphorylated histone H2AX (γH2AX) loci. The silencing of X-ray repair cross complementing group 1 (XRCC1), upregulated in B7-H3 overexpressing cells, induced an increase in cell death following oxaliplatin treatment. Finally, the upregulation of XRCC1 expression induced by B7-H3 involved PI3K-AKT pathway. In conclusion, B7-H3 promotes the oxaliplatin resistance in CRC cells upregulating the expression of XRCC1 via PI3K-AKT pathway.

Keywords: B7-H3; Colorectal cancer; Oxaliplatin resistance; PI3K-AKT pathway; XRCC1.

MeSH terms

Antineoplastic Agents / pharmacology*
B7 Antigens / genetics*
Cell Line, Tumor
Colon / drug effects
Colon / metabolism
Colon / pathology
Colorectal Neoplasms / drug therapy*
Colorectal Neoplasms / genetics
Colorectal Neoplasms / metabolism
Colorectal Neoplasms / pathology
DNA-Binding Proteins / genetics
Drug Resistance, Neoplasm*
Gene Expression Regulation, Neoplastic / drug effects
Humans
Organoplatinum Compounds / pharmacology*
Oxaliplatin
Phosphatidylinositol 3-Kinases / metabolism
Proto-Oncogene Proteins c-akt / metabolism
RNA Interference*
RNA, Small Interfering / genetics
Rectum / drug effects
Rectum / metabolism
Rectum / pathology
Signal Transduction / drug effects
X-ray Repair Cross Complementing Protein 1

Substances

Antineoplastic Agents
B7 Antigens
CD276 protein, human
DNA-Binding Proteins
Organoplatinum Compounds
RNA, Small Interfering
X-ray Repair Cross Complementing Protein 1
XRCC1 protein, human
Oxaliplatin
Phosphatidylinositol 3-Kinases
Proto-Oncogene Proteins c-akt