ABSTRACT
Objective: To investigate the effects of tetrandrine derivative HL-49 combined with cisplatin (DDP) or adriamycin (ADM) on the proliferation and apoptosis of triple-negative breast cancer MDAMB- 231 cells, and to explore the possible mechanism. Methods: MDA-MB -231 cells were treated with different concentrations of HL-49, DDP or ADM alone and HL-49 combined with DDP or ADM, respectively. The proliferation inhibitory rate of MDA-MB-231 cells was detected by MTT assay and the Q value was calculated. The colony forming ability of MDA-MB-231 cells was detected by plate cloning test. The apoptosis rate was detected by FCM method and the Q value was calculated. The expression levels of Bloom's symdrome helicase (BLM), breast cancer susceptibility gene 1 (BRCA1), DNA repair key enzyme Rad51, apoptosis-related protein caspase 3, caspase 8, caspase 10, Bax, p53 and Bcl-2 were detected by Western blotting. Results: The proliferation inhibitory rate of MDA-MB-231 cells in HL-49 combined with DDP or ADM group was significantly higher than that in HL-49, DDP or ADM alone group (all P < 0 05); the Q values of HL-49 (1 or 2 μmol/L) combined with DDP (5 or 10 μmol/L) were 2.04, 1.88, 1.87 and 1.83, respectively; while the Q values of HL-49 (1 or 2 μmol/L) combined with ADM (2 or 5 μmol/L) were 1.37, 1.21, 1.36 and 1.23, respectively. The colony formation number of MDA-MB-231 cells in HL-49 combined with DDP or ADM group was significantly lower than that in HL-49, DDP or ADM alone group (all P < 0 05). The apoptosis rate of MDA-MB-231 cells in HL-49 combined with DDP or ADM group was higher than that in HL-49, DDP or ADM alone group (all P < 0 05); the Q values of HL-49 (1 or 2 μmol/L) combined with DDP (5 or 10 μmol/L) were 1.20, 1.35, 1.70 and 2.06, respectively; the Q values of HL-49 (1 or 2 μmol/L) combined with ADM (2 or 5 μmol/L) were 1.48, 1.17, 1.99 and 2.13, respectively. The above results suggested that HL-49 and DDP (or ADM) had synergistic effects. As compared with HL-49, DDP or ADM alone group, the expression levels of caspase 3, caspase 8, caspase 10 and Bax proteins in HL-49 combined with DDP or ADM group were up-regulated, and the expression levels of Rad51, BRCA1, BLM, p53 and Bcl-2 proteins were down-regulated (all P < 0. 05). Conclusion: Tetrandrine derivative HL-49 combined with DDP or ADM has synergetic effect. The anti-tumor activity of the combination treatment is related to the induction of apoptosis in triple-negative breast cancer MDA-MB-231 cells.