title: Dexamethasone induces docetaxel and cisplatin resistance partially through up-regulating Krüppel-like factor 5 in triple-negative breast cancer.
abstract: OBJECTIVE
  Dexamethasone (Dex), a glucocorticoid (GC), is used as a pretreatment drug in cancer patients undergoing chemotherapy. Dex functions by binding to the glucocorticoid receptor (GR) to prevent allergic reactions and severe chemotherapeutic side effects such as nausea and vomiting. However, the mechanisms by which Dex causes chemoresistance remain unknown.
  
  
  METHODS
  We used docetaxel and cisplatin to treat triple-negative breast cancer (TNBC) cells with or without Dex and assessed cell proliferation using a sulforhodamine B colorimetric (SRB) assay. Additionally, Western blotting was employed to measure Krüppel-like factor 5 (KLF5), GR and several apoptosis-related proteins. To determine how the GR regulates KLF5, we used qRT-PCR, luciferase reporter assays and ChIP assays. Finally, we detected the involvement of Dex in TNBC chemotherapeutic resistance using HCC1806 xenograft model in vivo.
  
  
  RESULTS
  In this study, we demonstrated that Dex induces docetaxel and cisplatin resistance in TNBC cells in vitro and in vivo. Dex up-regulates pro-survival transcription factor KLF5 expression at both mRNA and protein levels dependent on GR. Importantly, Dex failed to promote cancer cell survival and tumor growth when KLF5 induction was blocked.
  
  
  CONCLUSIONS
  We conclude that KLF5 is a Dex-induced gene that contributes to Dex-mediated drug chemoresistance, providing a potential novel target for TNBC treatment.
authors.affiliation: Department of Gastrointestinal and Hernia Surgery, Institute of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, China.|Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan 650223, China.|Kunming Digestive Disease Treatment Engineering Technology Center, Kunming, Yunnan 650032, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Oncology, Yunnan Tumor Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650118, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Dong
authors.affiliation: Department of Breast Surgery, Yunnan Tumor Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650118, China.
authors.forename: Tianning
authors.initials: T
authors.lastname: Zou
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan 650223, China.
authors.forename: Chengzhi
authors.initials: C
authors.lastname: Du
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan 650223, China.
authors.forename: Siyuan
authors.initials: S
authors.lastname: Li
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan 650223, China.
authors.forename: Ceshi
authors.initials: C
authors.lastname: Chen
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan 650223, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Gastrointestinal and Hernia Surgery, Institute of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, China.|Kunming Digestive Disease Treatment Engineering Technology Center, Kunming, Yunnan 650032, China.
authors.forename: Kunhua
authors.initials: K
authors.lastname: Wang
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002945:Cisplatin / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D043823:Taxoids / Q000494:pharmacology*; D015854:Up-Regulation
chemical_list: D000893:Anti-Inflammatory Agents; D051741:Kruppel-Like Transcription Factors; D043823:Taxoids; D000077143:Docetaxel; D003907:Dexamethasone; D002945:Cisplatin
keywords: Dex; GR; KLF5; TNBC; drug resistance