Abstract

BACKGROUND: Dose-related toxicity is the major restriction of cisplatin and cisplatin-combination chemotherapy, and is a challenge for advanced gastric cancer treatment. We explored the possibility of using Paris saponin I as an agent to sensitize gastric cancer cells to cisplatin, and examined the underlying mechanism.

MATERIAL AND METHODS: Growth inhibition was detected by MTT assay. The cell cycle and apoptosis were detected using flow cytometry and Annexin V/PI staining. The P21waf1/cip1, Bcl-2, Bax, and caspase-3 protein expression were detected using Western blot analysis.

RESULTS: The results revealed that PSI sensitized gastric cancer cells to cisplatin, with low toxicity. The IC50 value of cisplatin in SGC-7901 cell lines was decreased when combined with PSI. PSI promoted cisplatin-induced G2/M phase arrest and apoptosis in a cisplatin concentration-dependent manner. Bcl-2 protein expression decreased, but Bax, caspase-3, and P21waf1/cip1 protein expression increased with PSI treatment.

CONCLUSIONS: The underlying mechanism of Paris saponin I may be related to targeting the apoptosis pathway and cell cycle blocking, which suggests that PSI is a potential therapeutic sensitizer for cisplatin in treating gastric cancer.

Keywords: Antineoplastic Combined Chemotherapy Protocols - pharmacology, Cell Cycle - drug effects, Cell Cycle Checkpoints - drug effects, Cell Proliferation - drug effects, Cell Survival - drug effects, Cisplatin - pharmacology, Diosgenin - pharmacology, Drug Synergism, Proto-Oncogene Proteins c-bcl-2 - metabolism, Saponins - pharmacology, bcl-2-Associated X Protein - metabolism