Abstract: OBJECTIVE: To evaluate the effects of tetrandrine plus arsenic trioxide on HCC1937 cells, a triple negative breast cancer cell line, and to explore possible mechanisms.METHODS: The 3-(4,5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide method was used to compare the antiproliferative effects of tetrandrine,arsenic trioxide alone and tetrandrine plus arsenic trioxide on HCC1937 cells. The median-effect principle(Chou-Talalay combination index method) was used to examine the interaction between the two drugs. Flow cytometry was used to evaluate effects of treatment with tetrandrine, arsenic trioxide or the combination of both on HCC1937 cell apoptosis. Real-time polymerase chain reaction and western blotting were performed to evaluate changes in apoptosis-related gene expression and protein levels.RESULTS: Tetrandrine and arsenic trioxide each in-hibited HCC1937 cell proliferation in a dose-dependent manner. The cell inhibition rate of HCC1937 cells treated with a combination of tetrandrine and arsenic trioxide was significantly higher than with either compound alone. The two drugs produced a synergistic effect when the inhibition rate was20%-40%. Flow cytometry results showed that treatment with the two drugs increased the proportion of apoptotic cells. In the combination treated group, caspase-3 activation and PARP cleavage were significantly higher than in the other groups.Moreover, Bcl-2 and survivin expression were decreased, whereas that of both Bid and Bax was increased.CONCLUSION: These findings demonstrated that tetrandrine plus arsenic trioxide had synergistic efficacy on induction of apoptosis in HCC1937 cells.

Key words: Triple negative breast neoplasms, Tetrandrine, Arsenicum sublimatum, HCC1937, Synergistic effect