Silencing of SIVA‑1 promotes cisplatin resistance in gastric cancer via the Bcl‑2/BAX‑mediated mitochondria‑dependent apoptosis pathway.

The aim of the present study was to investigate the effects of SIVA‑1 silencing on the drug resistance and biological functions of cisplatin (DDP)‑resistant human gastric cancer cells (AGS/DDP), and to explore the mechanism underlying its occurrence. AGS/DDP cells with stable silencing of SIVA‑1 were established by molecular biology techniques. The Cell Counting Kit‑8 assay was used to investigate the effect of SIVA‑1 silencing on drug sensitivity in AGS/DDP cells by measuring the IC(50) of Adriamycin, DDP and vincristine. The findings demonstrated that the suppression of SIVA‑1 in AGS/DDP cells markedly augmented the resistance to DDP. In addition, cell proliferation, cell migration, cell invasion and cell apoptosis were assessed using colony formation, cell scratch, Transwell and cell apoptosis assays, respectively. The results of these assays demonstrated that silencing SIVA‑1 notably increased the proliferation, migration and invasion of AGS/DDP cells, while concurrently inhibiting their apoptosis. Furthermore, the effects of SIVA‑1 silencing on drug‑resistant gastric cancer cells in vivo were confirmed using a subcutaneous xenograft model in nude mice. The results demonstrated that silencing SIVA‑1 led to a notable increase in tumor volume, growth rate and weight. The bioinformatics analyses results indicated that SIVA‑1 may have an interactive relationship with Bcl‑2, BAX, X‑linked inhibitor of apoptosis protein (XIAP), MAPK8 and baculoviral inhibitor of apoptosis repeat‑containing 5 (BIRC5), and could participate in the mitochondria‑dependent apoptosis pathway. The results of reverse transcription‑quantitative PCR and western blotting indicated that silencing SIVA‑1 in AGS/DDP cells promoted the expression levels of Bcl‑2, XIAP, MAPK8 and BIRC5, and inhibited the expression levels of BAX. In conclusion, silencing SIVA‑1 has been shown to modify sensitivity to DDP and biological function in drug‑resistant gastric cancer cells, either directly or indirectly. This phenomenon may be associated with the Bcl‑2/BAX‑mediated, mitochondria‑dependent apoptosis pathway.