Tanshinone IIA blocks epithelial-mesenchymal transition through HIF-1α downregulation, reversing hypoxia-induced chemotherapy resistance in breast cancer cell lines
Tanshinone IIA blocks epithelial-mesenchymal transition through HIF-1α downregulation, reversing hypoxia-induced chemotherapy resistance in breast cancer cell lines
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DOI：
10.3892/or.2014.3140
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发表时间：
2014-06-01
期刊：
影响因子：
4.2
通讯作者：
Liu, Yu
中科院分区：
文献类型：
--
作者：
Fu, Peifen;Du, Feiya;Liu, Yu
本研究旨在探讨丹参有效成分丹参酮HA（Tanshinone HA，Tan HA）对乳腺癌细胞上皮间质转化（epithelial-mesenchymal transition，EMT）和缺氧诱导的化疗耐药的影响。为了诱导缺氧，MCF-7和HCC 1973细胞用100 μ M去铁胺处理，然后用阿霉素（DOX）处理。分别使用CCK-8和EdU测定法检查细胞活力和增殖。免疫印迹和免疫荧光分析的两个EMT标志物，E-cadherin和波形蛋白的表达进行了。通过siRNA确定HIF-1 α和TWIST在介导Tan HA作用中的作用。基于该结果，在MCF-7和HCC 1973细胞中均观察到缺氧诱导的DOX抗性（均P=0.001），其被Tan HA逆转。具体地说，在缺氧条件下，Tan HA显著降低细胞活力和增殖（所有P
The aim of the present study was to investigate the effects of tanshinone HA (Tan HA), an active constituent of Salvia miltiorrhiza Bunge, on epithelial-mesenchymal transition (EMT) and hypoxia-induced chemoresistance in breast cancer cells. To induce hypoxia, MCF-7 and HCC1973 cells were treated with 100 mu M deferoxamine followed by doxorubicin (DOX). Cell viability and proliferation were examined using the CCK-8 and EdU assays, respectively. Western blot and immunofiuorescence analyses of the expression of two EMT markers, E-cadherin and vimentin, were also carried out. The role of HIF-1 alpha and TWIST in mediating the effects of Tan HA was determined through siRNA. Based on the results, hypoxia-induced DOX resistance was observed in both MCF-7 and HCC1973 cells (both P=0.001), which was reversed with Tan HA. Specifically, in hypoxic conditions, Tan HA significantly decreased cell viability and proliferation (all P