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Article
Metformin Reverses Prostate Cancer Resistance to Enzalutamide by Targeting TGF-β1/STAT3 Axis-Regulated EMT.
Cell Death & Disease
  • Qiuli Liu
  • Dali Tong
  • Gaolei Liu
  • Jing Xu
  • Khang Do
  • Kyla Geary
  • Dianzheng Zhang, Philadelphia College of Osteopathic Medicine
  • Jun Zhang
  • Yao Zhang
  • Yaoming Li
  • Gang Bi
  • Weihua Lan
  • Jun Jiang
Document Type
Article
Publication Date
8-24-2017
Abstract
Although the newly developed second-generation anti-androgen drug enzalutamide can repress prostate cancer progression significantly, it only extends the survival of prostate cancer patients by 4-6 months mainly due to the occurrence of enzalutamide resistance. Most of the previous studies on AR antagonist resistance have been focused on AR signaling. Therefore, the non-AR pathways on enzalutamide resistance remain largely unknown. By using C4-2, CWR22Rv1 and LNCaP cell lines, as well as mice bearing CWR22Rv1 xenografts treated with either enzalutamide or metformin alone or in combination, we demonstrated that metformin is capable of reversing enzalutamide resistance and restores sensitivity of CWR22Rv1 xenografts to enzalutamide. We showed that metformin alleviated resistance to enzalutamide by inhibiting EMT. Furthermore, based on the effect of metformin on the activation of STAT3 and expression of TGF-β1, we propose that metformin exerts its effects by targeting the TGF-β1/STAT3 axis. These findings suggest that combination of metformin with enzalutamide could be a more efficacious therapeutic strategy for the treatment of castration-resistant prostate cancer.
PubMed ID
28837141
Comments

This article was published in Cell Death & Disease, Volume 8.

The published version is available at http://dx.doi.org/10.1038/cddis.2017.417.

Copyright © 2017. (CC BY 4.0)

Citation Information
Qiuli Liu, Dali Tong, Gaolei Liu, Jing Xu, et al.. "Metformin Reverses Prostate Cancer Resistance to Enzalutamide by Targeting TGF-β1/STAT3 Axis-Regulated EMT." Cell Death & Disease Vol. 8 (2017)
Available at: http://works.bepress.com/dianzheng_zhang/55/