Dexamethasone induces docetaxel and cisplatin resistance partially through up-regulating Krüppel-like factor 5 in triple-negative breast cancer
文献类型:期刊论文
作者 | Li Z1,2,3; Dong J4; Chen CS[*]2; Liu R[*]2; Wang KH[*]1,3; Zou TN5; Du CZ2; Li SY2 |
刊名 | Oncotarget
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出版日期 | 2016 |
卷号 | X期号:X页码:XX-XX |
关键词 | Dex GR KLF5 TNBC drug resistance |
通讯作者 | wkh1963@yeah.net ; liurong@mail.kiz.ac.cn ; chenc@mail.kiz.ac.cn |
合作状况 | 其它 |
英文摘要 | 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. |
收录类别 | SCI |
资助信息 | This study was supported by the National Natural Science Foundation of China (No. 81322038 and 81272930 to R.L., No. 81325016 and 81120108019 to C.C.), the Yunnan Applied Basic Research Key Projects (2015FA027 to R.L.), the West Light Foundation of Chinese Academy of Sciences (to R.L.), the Youth Innovation Promotion Association, the Chinese Academy of Sciences (to R.L.), the Scholarship Award for Excellent Doctoral Student Granted of Yunnan Province (to Z.L.), the Foundation of Leading Talent Program of Health and Family Planning Commission of Yunnan Province (No. L-201205 to K.W.), the Foundation of the Institute of Gastroenterology, Research Institutions attached to the Health and Family Planning Commission of Yunnan Province (2014NS122 to K.W.), and the Foundation of the Institute of Breast Surgery, Research Institutions attached to the Health and Family Planning Commission of Yunnan Province (2014NS022 to T.Z.) |
语种 | 英语 |
源URL | [http://159.226.149.26:8080/handle/152453/10781] ![]() |
专题 | 昆明动物研究所_肿瘤生物学 昆明动物研究所_动物模型与人类重大疾病机理重点实验室 |
作者单位 | 1.Department of Gastrointestinal and Hernia Surgery, Institute of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, China 2.Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan 650223, China 3.Kunming Digestive Disease Treatment Engineering Technology Center, Kunming, Yunnan 650032, China 4.Department of Oncology, Yunnan Tumor Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650118, China 5.Department of Breast Surgery, Yunnan Tumor Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650118, China |
推荐引用方式 GB/T 7714 | Li Z,Dong J,Chen CS[*],et al. Dexamethasone induces docetaxel and cisplatin resistance partially through up-regulating Krüppel-like factor 5 in triple-negative breast cancer[J]. Oncotarget,2016,X(X):XX-XX. |
APA | Li Z.,Dong J.,Chen CS[*].,Liu R[*].,Wang KH[*].,...&Li SY.(2016).Dexamethasone induces docetaxel and cisplatin resistance partially through up-regulating Krüppel-like factor 5 in triple-negative breast cancer.Oncotarget,X(X),XX-XX. |
MLA | Li Z,et al."Dexamethasone induces docetaxel and cisplatin resistance partially through up-regulating Krüppel-like factor 5 in triple-negative breast cancer".Oncotarget X.X(2016):XX-XX. |
入库方式: OAI收割
来源:昆明动物研究所
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