TY - JOUR AB - The aim of the present study was to investigate the effects of tanshinone IIA (Tan IIA), 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 µM deferoxamine followed by doxorubicin (DOX). Cell viability and proliferation were examined using the CCK-8 and EdU assays, respectively. Western blot and immunofluorescence analyses of the expression of two EMT markers, E-cadherin and vimentin, were also carried out. The role of HIF-1α and TWIST in mediating the effects of Tan IIA 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 IIA. Specifically, in hypoxic conditions, Tan IIA significantly decreased cell viability and proliferation (all P≤0.001), but not apoptosis. Hypoxia also significantly reduced E-cadherin and increased vimentin protein levels (P≤0.005), which returned to control levels with Tan IIA. In addition, silencing both HIF-1α and TWIST expression abrogated the effects of Tan IIA on cell viability. Taken together, Tan IIA ameliorated hypoxia-induced DOX resistance and EMT in breast cancer cell lines, which may be attributed to the downregulation of HIF-1α expression. Further in vivo studies, however, are required to fully elucidate the therapeutic potential of Tan IIA in increasing the sensitivity of breast cancer cells to chemotherapy. AD - Department of Breast Surgery Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China Department of Hepatobiliary and Pancreatic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China AU - Fu,Peifen AU - Du,Feiya AU - Chen,Wei AU - Yao,Minya AU - Lv,Kezhen AU - Liu,Yu DA - 2014/06/01 DO - 10.3892/or.2014.3140 EP - 2568 IS - 6 JO - Oncol Rep KW - breast cancer chemotherapy resistance HIF-1α hypoxia tanshinone IIA PY - 2014 SN - 1021-335X 1791-2431 SP - 2561 ST - Tanshinone IIA blocks epithelial-mesenchymal transition through HIF-1α downregulation, reversing hypoxia-induced chemotherapy resistance in breast cancer cell lines T2 - Oncology Reports TI - Tanshinone IIA blocks epithelial-mesenchymal transition through HIF-1α downregulation, reversing hypoxia-induced chemotherapy resistance in breast cancer cell lines UR - https://doi.org/10.3892/or.2014.3140 VL - 31 ER -