Oncology Reports, 2014, 32(4):1647-53.

Synergistic cytotoxic effect of genistein and doxorubicin on drug-resistant human breast cancer MCF-7/Adr cells

Jia-Peng Xue, Geng Wang, Zong-Bin Zhao, et al

Department of Endocrine and Vascular Surgery, Taihe Hospital, Hubei Medical College, Shiyan, Hubei 442000, P.R. China

The molecular mechanisms underlying genistein-mediated reversal of chemoresistance remains unknown. In the present study, we investigated the molecular mechanisms by which genistein overcomes chemoresistance and its effect on doxorubicin-induced cytotoxicity. Consistent with previous reports, genistein combined with doxorubicin had a synergistic effect on MCF-7/Adr cells, and genistein reduced the chemoresistance of these cells. Genistein treatment increased the intracellular accumulation of doxorubicin but did not influence P-gp function. The combination of genistein and doxorubicin significantly induced cell cycle arrest and apoptosis. Genistein treatment strongly inhibited HER2/neu but not MDR-1 expression at both the mRNA and protein levels. Therefore, our results demonstrated that genistein combined with doxorubicin had a synergistic effect on MCF-7/Adr cells, and the mechanisms likely involve an increase in the intracellular accumulation of doxorubicin and suppression of HER2/neu expression.

希腊《肿瘤学报告》，2014年10月

金雀异黄素和阿霉素对耐药性人体乳腺癌 MCF-7/Adr 细胞的协同毒害作用

薛佳鹏，王庚，赵宗斌，等

中国湖北省十堰市湖北医学院太和医院内分泌和血管外科

金雀异黄素介导逆转化疗耐药性的分子机制仍然未知。在本研究中，我们研究了金雀异黄素克服化疗耐药性以及对阿霉素导致的细胞毒性的影响的分子机制。与先前的报告一致，金雀异黄素联合阿霉素 对MCF-7/Adr 细胞具有协同效应，并且金雀异黄素降低了这些细胞的化疗耐药性。金雀异黄素治疗提高了细胞内阿霉素的积累，但并不影响 P-糖蛋白的功能。金雀异黄素和阿霉素的组合明显诱导了细胞周期阻滞和细胞凋亡。金雀异黄素治疗强烈抑制 了HER2/neu 而没有抑制MNR-1的 mRNA 和蛋白水平表达。因此，我们的研究结果表明，金雀异黄素联合阿霉素对 MCF-7/Adr 细胞具有协同效应，并且这种机制可能关系到阿霉素的细胞内积累增加和抑制 HER2/neu 的表达。