目的 探讨丹参酮Ⅱ_A对乳腺癌细胞阿霉素化疗敏感性的影响及相关机制。方法 分别用丹参酮Ⅱ_A、阿霉素、阿霉素+丹参酮Ⅱ_A干预人乳腺癌MCF-7和阿霉素耐药的MCF-7（MCF-7/dox）细胞，采用MTS法检测细胞增殖率，流式细胞术检测细胞凋亡率，划痕实验观察细胞迁移能力，Western blotting法检测腺瘤样结肠息肉易感蛋白（APC）、β-catenin、钙黏附蛋白E（E-cadherin）、基质金属蛋白酶-2（MMP-2）、MMP-9蛋白的表达。结果 丹参酮Ⅱ_A能明显增强阿霉素对MCF-7和MCF-7/dox细胞的增殖抑制、迁移抑制和诱导凋亡作用；与阿霉素敏感的MCF-7细胞比较，MCF-7/dox细胞中APC蛋白表达水平显著降低（P<0.05），β-catenin蛋白表达水平显著提高（P<0.05）；与单用阿霉素比较，阿霉素与丹参酮Ⅱ_A联合使用能明显上调MCF-7及MCF-7/dox细胞内APC及E-cadherin表达水平（P<0.05），下调β-catenin、MMP-2及MMP-9蛋白表达水平（P<0.05）。结论 APC/β-catenin信号通路参与了乳腺癌细胞阿霉素耐药的发生；丹参酮Ⅱ_A能够通过调控APC/β-catenin信号通路增强乳腺癌细胞对阿霉素化疗的敏感性。

Objective To assess the effect of tanshinone Ⅱ_A 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 Ⅱ_A, doxorubicin, and doxorubicin combined with tanshinone Ⅱ_A. 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 Ⅱ_A 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 Ⅱ_A 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 Ⅱ_A enhanced the chemosensitivity of doxorubicin in breast cancer cells through regulating APC/β-catenin pathway.

R285.5

国家自然科学基金资助项目（81303255）