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STAT5a Confers Doxorubicin Resistance to Breast Cancer by Regulating ABCB1

Zhaoqing Li1,2,3, Cong Chen2,3, Lini Chen2,3

  • 1Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Frontiers in Oncology
|August 2, 2021
PubMed

Insights

Signal transducer and activator of transcription (STAT) 5a drives chemoresistance in breast cancer by increasing ABCB1 expression. The drug pimozide effectively targets STAT5a, resensitizing resistant cells and offering a new therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Chemoresistance significantly impacts breast cancer patient outcomes.
  • The role of Signal transducer and activator of transcription (STAT) 5a in breast cancer and its link to chemoresistance are not well-understood.

Purpose of the Study:

  • To investigate the role of STAT5a in chemoresistance in breast cancer.
  • To identify STAT5a as a potential therapeutic target for overcoming doxorubicin resistance.
  • To evaluate the efficacy of pimozide in reversing chemoresistance.

Main Methods:

  • Comparative analysis of STAT5a and ABCB1 expression in sensitive vs. resistant breast cancer cell lines and patient samples.
  • Functional assays to determine the roles of STAT5a and ABCB1 in doxorubicin resistance.
  • In vitro and in vivo studies to assess the effect of pimozide on STAT5a activity and chemoresistance.

Main Results:

  • STAT5a and ABCB1 expression are elevated in doxorubicin-resistant breast cancer cells and patients, with a positive correlation.
  • STAT5a directly regulates ABCB1 transcription, contributing to doxorubicin resistance.
  • Pimozide inhibits STAT5a, resensitizes resistant breast cancer cells to doxorubicin in vitro, and shows efficacy in vivo.

Conclusions:

  • STAT5a is a key inducer of doxorubicin resistance in breast cancer.
  • Targeting STAT5a presents a promising strategy for treating chemoresistant breast cancer.
  • Repurposing the FDA-approved drug pimozide for doxorubicin resensitization is a viable therapeutic approach due to its safety profile.
Keywords:
ABCB1STAT5Abreast cancerdoxorubicin resistancepimozide

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