Tanshinone IIA blocks epithelial-mesenchymal transition through HIF-1α downregulation, reversing hypoxia-induced chemotherapy resistance in breast cancer cell lines

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 <= 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-1 alpha and TWIST expression abrogated the effects of Tan IIA on cell viability. Taken together, Tan HA ameliorated hypoxia-induced DOX resistance and EMT in breast cancer cell lines, which may be attributed to the downregulation of HIF-1 alpha 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.