Anti-tumor effect and its mechanism of arsenic trioxide combined with fluorouracil on human coloncarcinoma cell line Lovo

OBJECTIVE:To study the anti-tumor effect of arsenic trioxide(As_2O_3) combined with fluorouracil(5-FU) on the human coloncarcinoma cell line Lovo,and explore its mechanism.METHODS: In vitro ,human coloncarcinoma cell line Lovo was treated by As_2O_3 and 5-FU in various concentrations respectively alone or in combination,and then the cell growth was assayed by MTT method,apoptosis,morphological and periodic return changes were observed by acridine orange(AO)/ethidiumbromide(EB) fluorescent staining, DNA gel electrophoresis,electron microscopy detection and flow cytometry,and the expression of apoptosis-related genes were analyzed by immunohistochemical staining method. RESULTS: Compared with As_2O_3 or 5-FU individual drug groups, As_2O_3 combined with 5-FU obviously increased the inhibitatory rate and apoptosis rate of the human coloncarcinoma cell line Lovo.The cell cycle distribution was altered and the ratio of S phase and G_2/M phase cell decreased and the portion of G_0/G_1 phase cell increased following the treatment with As_2O_3 combined with 5-FU, with bcl-2 gene expression down-regulated,and bax and Fas gene expression up-regulated. CONCLUSION: Arsenic trioxide combined with 5-FU may obviously increase the anti-coloncarcinoma effect,and maybe its mechanism is increasing apoptosis-inducing effect which is regulated by several genes and enhancing anti-tumor effect of cell cycle specific agent combined with cell cycle regulatory agent.