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

  • Authors:
    • Peifen Fu
    • Feiya Du
    • Wei Chen
    • Minya Yao
    • Kezhen Lv
    • Yu Liu
  • View Affiliations

  • Published online on: April 16, 2014     https://doi.org/10.3892/or.2014.3140
  • Pages: 2561-2568
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Abstract

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.

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June 2014
Volume 31 Issue 6

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Copy and paste a formatted citation
APA
Fu, P., Du, F., Chen, W., Yao, M., Lv, K., & Liu, Y. (2014). Tanshinone IIA blocks epithelial-mesenchymal transition through HIF-1α downregulation, reversing hypoxia-induced chemotherapy resistance in breast cancer cell lines. Oncology Reports, 31, 2561-2568. https://doi.org/10.3892/or.2014.3140
MLA
Fu, P., Du, F., Chen, W., Yao, M., Lv, K., Liu, Y."Tanshinone IIA blocks epithelial-mesenchymal transition through HIF-1α downregulation, reversing hypoxia-induced chemotherapy resistance in breast cancer cell lines". Oncology Reports 31.6 (2014): 2561-2568.
Chicago
Fu, P., Du, F., Chen, W., Yao, M., Lv, K., Liu, Y."Tanshinone IIA blocks epithelial-mesenchymal transition through HIF-1α downregulation, reversing hypoxia-induced chemotherapy resistance in breast cancer cell lines". Oncology Reports 31, no. 6 (2014): 2561-2568. https://doi.org/10.3892/or.2014.3140