Research Papers:

Dexamethasone induces docetaxel and cisplatin resistance partially through up-regulating Krüppel-like factor 5 in triple-negative breast cancer

Zhen Li, Jian Dong, Tianning Zou, Chengzhi Du, Siyuan Li, Ceshi Chen, Rong Liu and Kunhua Wang _

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Oncotarget. 2017; 8:11555-11565. https://doi.org/10.18632/oncotarget.14135

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Zhen Li1,2,3,*, Jian Dong4,*, Tianning Zou5, Chengzhi Du2, Siyuan Li2, Ceshi Chen2, Rong Liu2, Kunhua Wang1,3

1Department of Gastrointestinal and Hernia Surgery, Institute of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, China

2Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan 650223, China

3Kunming Digestive Disease Treatment Engineering Technology Center, Kunming, Yunnan 650032, China

4Department of Oncology, Yunnan Tumor Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650118, China

5Department of Breast Surgery, Yunnan Tumor Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650118, China

*These authors have contributed equally to this work

Correspondence to:

Kunhua Wang, email: [email protected]

Rong Liu, email: [email protected]

Ceshi Chen, email: [email protected]

Keywords: Dex, GR, KLF5, TNBC, drug resistance

Received: July 18, 2016     Accepted: November 22, 2016     Published: December 24, 2016


Purpose: 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.

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