Arsenic trioxide inhibition of tumor growth of subcutaneously implanted human breast cancer cells and its mechanism

Objective To study the inhibitory effect of arsenic trioxide(As_2O_3) on the tumor growth of breast cancer cell line MCF-7 implanted subcutaneously in nude mice and its mechanism.Methods BALB/C-nu/nu nude mice were subcutaneously injected with MCF-7 breast cancer cell line,and treated with intraperitoneal injection of As_2O_3 and 5-FU in different concentrations.The implanted tumor was weighed,and the tumor inhibition rates were calculated.The apoptosis of the implanted tumor was detected by flow cytometry.The expressions of bcl-2 and Fas induced by As_2O_3 were examined by immunohistochemical method.Routine blood test and bone marrow test were used to observe the function of hematopoietic system after As_2O_3 treatment.Results The growth of implanted tumor was markedly inhibited with 5-FU,low dose and high dose As_2O_3,the inhibitory rates being 38.33%、51.42% and 62.43%,respectively.The inhibitory effect of As_2O_3 was significantly stronger than that of 5-FU(P0.01).The apoptosis rate of MCF-7 cells treated with the 2 concentrations of As_2O_2 was significantly higher than that of 5-FU treated group.Breast cancer cells in all the study groups showed G_2/M stage arrest,while a marked apoptosis peak was observed before the G_1 peak.The immunohistochemical staining showed that the number of bcl-2 protein positive cells decreased,and the number of Fas protein positive cells increased.The function of hematopoietic system was not inhibited.Conclusions As_2O_3 inhibits the growth of human breast cancer cell implanted tumor and induces apoptosis of MCF-7.The molecular mechanism of As_2O_3 on induction of apoptosis of breast cancer cells may be through decreasing the expression of bcl-2 and increasing the expression of Fas.