Cytotoxicity of Tanshinone IIA combined with Taxol on drug-resist breast cancer cells MCF-7 through inhibition of Tau

Cytotoxicity of Tanshinone IIA combined with Taxol on drug-resist breast cancer cells MCF-7 through inhibition of Tau
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DOI:
10.1002/ptr.6014
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发表时间:
2018-04-01
影响因子:
7.2
通讯作者:
Zhou, Peng
Zhou, Peng
中科院分区:
医学2区
文献类型:
--
作者:
Lin, Hui;Zheng, Luya;Zhou, Peng

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耐药是提高癌症患者总体疗效和生存的主要障碍。紫杉醇是乳腺癌最常用的化疗药物之一。与许多癌症治疗剂一样,在使用紫杉醇治疗恶性肿瘤时,耐药性仍然是一个重大问题。在本研究中,雌激素受体阳性的乳腺癌细胞MCF-7诱导紫杉醇耐药。选择丹参酮IIA联合紫杉醇治疗。在大多数药物浓度下,联合用药均表现出加性效应。耐药癌细胞表现出较高的微管相关蛋白(Tau)表达,这被认为是紫杉醇耐药的原因之一。丹参酮IIA抑制了MCF-7细胞中Tau的表达,提高了对紫杉醇的敏感性。此外,丹参酮IIA对MCF-7也表现出细胞毒性,这可能与其雌激素效应有关。综上所述,丹参酮IIA与紫杉醇联用对紫杉醇耐药的MCF-7细胞具有更高的细胞毒性,这可能与抑制Tau有关。
Drug resistance represents a major obstacle to improving the overall response and survival of cancer patients. Taxol is one of the most commonly used chemotherapy agents in breast cancer. As with many cancer therapeutic agents, resistance remains a significant problem when using Taxol to treat malignancies. In this study, estrogen receptor positive breast cancer cells MCF-7 were induced Taxol resistance. And Tanshinone IIA combined with Taxol was chosen to treat it. The drugs combination showed additive effect in most drug concentrations. Drug resistance cancer cells showed a higher microtubule associated protein (Tau) expression, which was considered as one of the reasons for Taxol resistance. Tanshinone IIA inhibited the expression of Tau in MCF-7 cells and resulted in higher sensibility of Taxol. Moreover, Tanshinone IIA also showed cytotoxicity to MCF-7, which might be related to its estrogenicity effect. In conclusion, the combination of Tanshinone IIA and Taxol showed higher cytotoxicity to Taxol resistant MCF-7 cells, which might be related to the inhibition of Tau.