Synergistic pro-apoptotic effect of triptolide combined with doxorubicin in human breast cancer cell line MCF-7

Abstract

Objective To study the effect of triptolide(TPL)combined with chemotherapy drug doxorubicin(DOX)on apoptosis of human breast cancer cell line MCF-7 and its molecular mechanism. Methods MCF-7 cells were treated with triptolide and different concentrations of doxorubicin alone or in combination. Cell viability was analyzed by CCK-8 method with the combination index calculated. Cell proliferation was detected by plate cloning formation assay. Cell apoptosis and cell cycle were detected by flow cytometry. The expressions of apoptosis-related proteins Bcl-2, Bax, cleaved caspase-3 and proteins in PI3K/AKT signaling pathway were analyzed by Western blot. Results Triptolide combined with different concentrations of doxorubicin significantly inhibited cell proliferation as compared with the doxorubicin group alone after incubation for 24, 48 and 72 hours(P＜0.05). The clone formation was restrained and the cell apoptosis rate was significantly higher(P＜0.01). The expressions of Bax and cleaved caspase-3 was up-regulated, and the expressions of Bcl-2, p-PI3K, p-AKT was down-regulated(P＜0.05). The cells were blocked in S phase after combination treatment of the two drugs(P＜0.05). Conclusions The combination of triptolide and doxorubicin significantly increases the sensitivity of MCF-7 cells to doxorubicin and promotes the apoptosis of cells, which might be related to the inhibition of PI3K/AKT signaling pathway.

Keywords

• triptolide|doxorubicin|breast cancer|combination therapy|apoptosis