Objective To investigate the effects and mechanisms of tanshinone ⅡA on the chemosensitivity of human breast cancer MCF-7 and MDA-MB-231 cells to doxorubicin.
Methods Human breast cancer MCF-7 and MDA-MB-231 cells were treated with different concentrations of tanshinone ⅡA. The effect of tanshinone ⅡA on the proliferation of MCF-7 and MDA-MB-231 cells were assessed by MTS assay, and nontoxic dose of tanshinone ⅡA was screened. MCF-7 and MDA-MB-231 cells were exposed to different concentrations of doxorubicin with or without nontoxic dose of tanshinone ⅡA intervention. Cell proliferation was measured by MTS assay; cell apoptotic rate, the expression of CD44+/CD24-/low as a surface marker of breast cancer stem cells and intracellular doxorubicin accumulation were analyzed by flow cytometry; the expressions of P-gp, BCRP and MRP1 were detected by Western blot.
Results Tanshinone ⅡA inhibited the proliferation of MCF-7 and MDA-MB-231 cells in a dose-dependent manner; compared with doxorubicin alone, MCF-7 and MDA-MB-231 cells treated with doxorubicin combined with nontoxic dose of tanshinone ⅡA exhibited a slower growth rate; nontoxic doses of tanshinone ⅡA significantly enhanced the abilities of doxorubicin to induce the apoptosis of breast cancer cells (all P < 0.05) and kill breast cancer stem cells (P=0.048), promoted the accumulations of doxorubicin in breast cancer cells (all P < 0.05) and down-regulated the expressions of P-gp, BCRP and MRP1 in doxorubicin-treated breast cancer cells (all P < 0.05).
Conclusion Tanshinone ⅡA could enhance the chemosensitivity of breast cancer cells to doxorubicin, and the mechanism may be related to the down-regulation of P-gp, BCRP and MRP1 expression.
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