Anti-tumor Effect And Its Mechanism Of Arsenic Trioxide Combined With Fluorouracil On Human Gastric Cancer Cell Line SGC-7901 In Vitro

Objective As one of the most common malignant tumors in China, Gastric cancer lacks early detective and effective curing methods, especially to intermediate or advanced stage ones. Arsenic trioxide (As₂O₃) has shown obvious anti-tumor effect both in vitro and in animal experiments, and the mechanisms are related to cell cycle blocking and apoptosis-inducing effects. To provide theoretical proof for new curative chemotherapy drugs and combination chemotherapy programs in clinic, we treated human gastric cancer cell line SGC-7901 with As₂O₃ combined with the traditional chemotherapy drug: Fluorouracil, and observed cell apoptosis rate, the changes of the cell cycle and the expression of apoptosis -related gene.Methods In vitro, human gastric cancer cell line SGC-7901 in log phase was intervened by As₂O₃ (final concentrations in order:1.0,5.0,10.0μmol/L) and 5-Fu (final concentration:50mg/L) respectively alone or in combination, and incubated for 24h, 48h, 72h. Blank group is set up. The cell apoptosis and cell cycle changes were observed by flow cytometry (FCM), and the expression of apoptosis-related gene Bcl-2 was analyzed by immunocytochemical method (PV method) and absolute gray scales quantitative method.Result Both As₂O₃ and 5-Fu can significantly increase the apoptosis rates of gastric cells. Compared with using alone, the combination of the two drugs can increase the apoptosis rates more obviously(P<0.01), and the apoptosis rate was related to the dose and acting time of As₂O₃(P<0.01). Cell cycle analysis showed that the cells in G0/G1 period cells increased (P<0.01) and S decreased(P < 0.01). Bcl-2 expressed at cell membranes or in cytoplasm, shown as buffy particles. Gray scales quantitative analysis showed that the Bcl-2 expression of combined groups was obviously less than using alone(P<0.01). The Bcl-2 expression was related to the dose and acting time of As₂O₃(P <0.01;p<0.05),but there is no difference between 24h and 48h(p > 0.05).The expressions of Bcl-2 intervened by drugs were all lower than blank group(P<0.01). Conclusion As₂O₃ combined with 5-Fu has synergistic effects on SGC-7901, and the mechanisms may be related to cell cycle blocking and apoptosis-inducing effects through regulating expression of related genes Bcl-2.