miR‑494‑BAG‑1 axis is involved in cinobufacini‑induced cell proliferation and apoptosis in gastric cancer.

Cinobufacini is widely used in the treatment of advanced cancers. It has been previously reported that microRNA (miR)-494 was upregulated in cinobufacini-treated gastric cancer cells; however, the detailed role of miR-494 in the anti-tumor activity of cinobufacini is unclear. The present study aimed to clarify the function of miR-494 in cinobufacini-induced cell behavior changes. Cell viability and proliferation ability were investigated using a Cell Counting Kit-8 assay. Flow cytometry was performed to investigate the apoptosis rate of gastric cancer (GC) cells. The mRNA expression levels of microRNA (miR)-494 and BCL2 associated athanogene 1 (BAG-1) were investigated using reverse transcription-quantitative polymerase chain reaction, and the protein expression level of BAG-1 was investigated using western blot assays. The results demonstrated that treatment with cinobufacini suppressed proliferation and promoted apoptosis of gastric cancer cells. miR-494 acts as a tumor suppressor gene in gastric cancer. In cinobufacini-treated cells, miR-494 and BAG-1 exhibited opposing expression trends. Furthermore, knockdown of miR-494 in cinobufacini-treated cells upregulated the protein expression level of BAG-1, promoted cell proliferation and inhibited cell apoptosis. In addition, inhibition of BAG-1 using small interfering RNA in cinobufacini-treated cells partially abrogated the effects of miR-494 inhibitor on cell proliferation and apoptosis. Thus, these results suggest that cinobufacini suppresses GC cells proliferation and promotes apoptosis partially through the regulation of miR-494-BAG-1 axis, which may provide a novel insight into the functional mechanism of cinobufacini.