2. Academic Validation
  3. PLCε knockdown overcomes drug resistance to androgen receptor antagonist in castration-resistant prostate cancer by suppressing the wnt3a/β-catenin pathway

PLCε knockdown overcomes drug resistance to androgen receptor antagonist in castration-resistant prostate cancer by suppressing the wnt3a/β-catenin pathway

  • J Cell Physiol. 2019 Jan 26. doi: 10.1002/jcp.28195.
Luo Li 1,  Zhongbo Du 2 3,  Yingying Gao 4,  Yu Tang 5,  Yanru Fan 1,  Wei Sun 6,  Ting Li 1,  Nanjing Liu 1,  Mengjuan Yuan 6,  Jiaxin Fan 1,  Lingfang Niu 1,  Jinxiao Yan 1,  Limei Duan 1,  Xiaohou Wu 7,  Chunli Luo 1
Affiliations

Affiliations

  • 1 Key Laboratory of Diagnostics Medicine Designated by the Ministry of Education, Chongqing Medical University, Chongqing, China.
  • 2 Department of Clinical Medicine, North Sichuan Medical College, Nanchong, China.
  • 3 Department of Urology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.
  • 4 Department of Clinical Laboratory, Jiamusi University Clinical Medical College, Jiamusi, China.
  • 5 State key Laboratory of Ultrasound Engineering in Medicine Co-Founded by Chongqing and the Ministry of Science and Technology, Biomedical Engineering College, Chongqing Medical University, Chongqing, China.
  • 6 Department of Urology, Fuling Center Hospital of Chongqing, Chongqing, China.
  • 7 Department of Urology, First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
PMID: 30684266 DOI: 10.1002/jcp.28195
Abstract

Most prostate cancers (Pcas) develop into castration-resistant prostate Cancer (CRPC) after receiving androgen deprivation therapy (ADT). The expression levels of PLCε and wnt3a are increased in Pca and regulate Androgen Receptor (AR) activity. However, the biological function and mechanisms of PLCε and wnt3a in CRPC remain unknown. In this study, we found that the expression levels of PLCε, wnt3a, and AR were significantly increased in CRPC tissues as well as bicalutamide-resistant-LNCaP and enzalutamide-resistant-LNCaP cells. In addition, PLCε knockdown partly restored the sensitivity of drug-resistant cells to bicalutamide and enzalutamide by inhibiting the activity of the wnt3a/β-catenin/AR signaling axis. Interestingly, the resistance of LNCaP cells docetaxel is related to PLCε but not the wnt3a/β-catenin pathway. We also found that the combination of PLCε knockdown and enzalutamide treatment synergistically suppressed cell proliferation, tumor growth, and bone metastasis using in vitro and in vivo experiments. Our study revealed that PLCε is involved in the progression of drug-resistance in CRPC and could be a new target for the treatment of CRPC.

Keywords

CRPC; PLCε; bicalutamide; docetaxel; enzalutamide; proliferation and bone metastasis; wnt3a.

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