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PLCε knockdown overcomes drug resistance to androgen receptor antagonist in castration‐resistant prostate cancer by suppressing the wnt3a/β‐catenin pathway
Author(s) -
Li Luo,
Du Zhongbo,
Gao Yingying,
Tang Yu,
Fan Yanru,
Sun Wei,
Li Ting,
Liu Nanjing,
Yuan Mengjuan,
Fan Jiaxin,
Niu Lingfang,
Yan Jinxiao,
Duan Limei,
Wu Xiaohou,
Luo Chunli
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.28195
Subject(s) - prostate cancer , androgen receptor , gene knockdown , antagonist , androgen , medicine , prostate , testosterone (patch) , androgen receptor antagonists , cancer research , drug resistance , cancer , pharmacology , receptor , biology , hormone , apoptosis , biochemistry , microbiology and biotechnology
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.