Cooperative Treatment of Gastric Cancer Using B7-H7 siRNA and Docetaxel; How Could They Modify Their Effectiveness?

Abstract

Purpose: Despite the high prevalence of gastric cancer (GC), drug resistance is a major problem for effective chemotherapy. B7-H7 is a novel member of the B7 superfamily and is expressed in most common cancers. However, the role of B7-H7 on the aggressiveness of GC and chemo-sensitivity has remained unknown. Therefore, this study was designed to assess the effect of B7-H7 suppression using small interference RNA (siRNA) in combination with Docetaxel on GC cells. Methods: MTT test was applied to determine the IC50 of Docetaxel and the combined effect of B7-H7 siRNA and Docetaxel on the viability of the MKN-45 cells. To determine B7-H7, BCL-2, BAX, and Caspase-3-8-9 genes expression, qRT-PCR was performed. Furthermore, flow cytometry was applied to evaluate apoptosis and the cell cycle status. Finally, to evaluate the effect of this combination therapy on migratory capacity and colony‑forming ability, wound healing assay and colony formation test were employed, respectively. Results: B7-H7 suppression increased the chemo-sensitivity of MKN-45 cells to Docetaxel. The expression of B7-H7 mRNA was reduced after using B7-H7 siRNA and Docetaxel in MKN-45 GC cells. Also, B7-H7 suppression alongside Docetaxel reduced cell migration and colony formation rate, arrested the cell cycle at the G2-M phase, and induced apoptosis by modulating the expression of apoptotic target genes. Conclusion: B7-H7 plays a significant role in the chemo-sensitivity and pathogenesis of GC. Therefore, B7-H7 suppression, in combination with Docetaxel, may be a promising therapeutic approach in treating GC.