Effect of tanshinone IIA on chemosensitivity of doxorubicin in breast cancer cells and its related mechanisms / 中草药

ABSTRACT

Objective To assess the effect of tanshinone IIA on the chemosensitivity of doxorubicin in breast cancer cells and investigate its related mechanisms. Methods MCF-7 and MCF-7/dox cells were respectively treated with tanshinone IIA, doxorubicin, and doxorubicin combined with tanshinone IIA. MTS assay was used to detect cell proliferation; Flow cytometry was used to analyze cell apoptosis; Scratch assay was used to evaluate cell migration; Western blotting was used to detect the expressions of APC, β-catenin, E-cadherin, MMP-2, and MMP-9. Results Tanshinone IIA could significantly enhance the inhibitory effects of doxorubicin on cell proliferation and migration of MCF-7 and MCF-7/dox cells and the effect of doxorubicin on inducing cell apoptosis. Compared to MCF-7 cells, the protein expression of APC in MCF-7/dox cells was significantly decreased (P < 0.05) while the expression of β-catenin in MCF-7/dox cells was significantly increased (P < 0.05). Compared to treatment with doxorubicin alone, combined treatment of doxorubicin and tanshinone IIA could significantly up-regulate the protein expression of APC and E-cadherin (P < 0.05) and down-regulate the protein expression of β-catenin, MMP-2, and MMP-9 (P < 0.05). Conclusion The APC/β-catenin pathway was involved in the development of doxorubicin resistance in breast cancer cells. Tanshinone IIA enhanced the chemosensitivity of doxorubicin in breast cancer cells through regulating APC/β-catenin pathway.