Frontiers in Oncology (Jul 2021)
STAT5a Confers Doxorubicin Resistance to Breast Cancer by Regulating ABCB1
- Zhaoqing Li,
- Zhaoqing Li,
- Zhaoqing Li,
- Cong Chen,
- Cong Chen,
- Lini Chen,
- Lini Chen,
- Dengdi Hu,
- Dengdi Hu,
- Dengdi Hu,
- Xiqian Yang,
- Xiqian Yang,
- Xiqian Yang,
- Wenying Zhuo,
- Wenying Zhuo,
- Wenying Zhuo,
- Yongxia Chen,
- Yongxia Chen,
- Jingjing Yang,
- Jingjing Yang,
- Yulu Zhou,
- Yulu Zhou,
- Misha Mao,
- Misha Mao,
- Xun Zhang,
- Xun Zhang,
- Ling Xu,
- Ling Xu,
- Siwei Ju,
- Siwei Ju,
- Jun Shen,
- Jun Shen,
- Qinchuan Wang,
- Qinchuan Wang,
- Minjun Dong,
- Minjun Dong,
- Shuduo Xie,
- Shuduo Xie,
- Qun Wei,
- Qun Wei,
- Yunlu Jia,
- Jichun Zhou,
- Jichun Zhou,
- Linbo Wang,
- Linbo Wang
Affiliations
- Zhaoqing Li
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Zhaoqing Li
- Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China
- Zhaoqing Li
- Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China
- Cong Chen
- Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China
- Cong Chen
- Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China
- Lini Chen
- Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China
- Lini Chen
- Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China
- Dengdi Hu
- Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China
- Dengdi Hu
- Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China
- Dengdi Hu
- Affiliated Cixi Hospital, Wenzhou Medical University, Ningbo, China
- Xiqian Yang
- Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China
- Xiqian Yang
- Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China
- Xiqian Yang
- Breast Surgical Department, Shaoxing Maternity and Child Health Care Hospital, Shaoxing, China
- Wenying Zhuo
- Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China
- Wenying Zhuo
- Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China
- Wenying Zhuo
- Affiliated Cixi Hospital, Wenzhou Medical University, Ningbo, China
- Yongxia Chen
- Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China
- Yongxia Chen
- Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China
- Jingjing Yang
- Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China
- Jingjing Yang
- Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China
- Yulu Zhou
- Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China
- Yulu Zhou
- Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China
- Misha Mao
- Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China
- Misha Mao
- Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China
- Xun Zhang
- Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China
- Xun Zhang
- Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China
- Ling Xu
- Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China
- Ling Xu
- Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China
- Siwei Ju
- Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China
- Siwei Ju
- Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China
- Jun Shen
- Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China
- Jun Shen
- Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China
- Qinchuan Wang
- Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China
- Qinchuan Wang
- Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China
- Minjun Dong
- Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China
- Minjun Dong
- Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China
- Shuduo Xie
- Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China
- Shuduo Xie
- Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China
- Qun Wei
- Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China
- Qun Wei
- Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China
- Yunlu Jia
- The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Jichun Zhou
- Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China
- Jichun Zhou
- Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China
- Linbo Wang
- Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China
- Linbo Wang
- Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China
- DOI
- https://doi.org/10.3389/fonc.2021.697950
- Journal volume & issue
-
Vol. 11
Abstract
Chemoresistance is a daunting challenge to the prognosis of patients with breast cancer. Signal transducer and activator of transcription (STAT) 5a plays vital roles in the development of various cancers, but its function in breast cancer is controversial, and its role in chemoresistance in breast cancer remains unexplored. Here we identified STAT5a as a chemoresistance inducer that regulates the expression of ABCB1 in breast cancer and can be targeted by pimozide, an FDA-approved psychotropic drug. First, we found that STAT5a and ABCB1 were expressed at higher levels in doxorubicin-resistant cell lines and chemoresistant patients, and their expression was positively correlated. Then, we confirmed the essential roles of STAT5a and ABCB1 in doxorubicin resistance in breast cancer cells and the regulation of ABCB1 transcription by STAT5a. Subsequently, the efficacy of pimozide in inhibiting STAT5a and sensitizing doxorubicin-resistant breast cancer cells was tested. Finally, we verified the role of STAT5a in doxorubicin resistance in breast cancer and the efficacy of pimozide in reversing this resistance in vivo. Our study demonstrated the vital role of STAT5a in doxorubicin resistance in breast cancer. Targeting STAT5a might be a promising strategy for treating doxorubicin-resistant breast cancer. Moreover, repurposing pimozide for doxorubicin resensitization is attractive due to the safety profile of pimozide.
Keywords
