title: Tanshinone IIA blocks epithelial-mesenchymal transition through HIF-1α downregulation, reversing hypoxia-induced chemotherapy resistance in breast cancer cell lines.
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.
authors.affiliation: Department of Breast Surgery Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Peifen
authors.initials: P
authors.lastname: Fu
authors.affiliation: Department of Breast Surgery Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Feiya
authors.initials: F
authors.lastname: Du
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Breast Surgery Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Minya
authors.initials: M
authors.lastname: Yao
authors.affiliation: Department of Breast Surgery Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Kezhen
authors.initials: K
authors.lastname: Lv
authors.affiliation: Department of Breast Surgery Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
mesh_terms: D045784:Abietanes / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D015687:Cell Hypoxia / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis*; D061986:MCF-7 Cells
chemical_list: D045784:Abietanes; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C021751:tanshinone