Abstract

Cancer of the stomach is one of the most frequent forms of cancer in adults. The treatment for gastric cancer with cisplatin brought a serious side effect of drug resistance. Cinobufagin could reverse the side effect still remains unknown. The object of the current research was to examine the role of cinobufagin in reversing the resistance of cisplatin in treatment of gastric cancer. Drug screening was used to isolate the cisplatin-resistant SGC7901-DDP cell line. The pathway variation in SGC7901-DDP was assayed by Western blot. Then, the cell line SGC7901-DDP was subjected to hypoxia treatment. The cell viability and apoptosis proportion was examined in hypoxia treatment. In addition, the underlying mechanism was explored by probing the protein kinase B/mammalian target of rapamycin signal pathway. Furthermore, the antagonistic action of cinobufagin on the cell line SGC7901-DDP was examined by three different treatments on SDC7901-DDP cell line. After treatments, the cell viability, the apoptosis proportion and protein kinase B/mammalian target of rapamycin signal pathway was assayed respectively by cell counting kit-8, flow cytometer and Western blot. The results indicated that the cells in the hypoxia+cinobufagin group were less likely to survive than cells in the other three groups. In addition, the western operation illustrated that the protein kinase B/mammalian target of rapamycin pathway and hypoxia-inducible factor-alpha factor was inhibited in cinobufagin+hypoxia group compared to that in hypoxia group. The results indicated that cinobufagin could decrease the cell viability, increase the apoptosis proportion and reverse the cisplatin resistance in SGC7901-DDP cell line by protein kinase B/mammalian target of rapamycin signal pathway. Lastly, the in vitro assay was completed and the result demonstrated that cinobufagin could inhibit the lump growth and reverse the cisplatin resistance. The cinobufagin could reverse the cisplatin resistance for gastric cancer therapy through protein kinase B/mammalian target of rapamycin signal pathway.