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Exendin‐4 enhances radiation response of prostate cancer
Author(s) -
He Wenjing,
Li Junhe
Publication year - 2018
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.23687
Subject(s) - lncap , prostate cancer , ampk , cancer research , pi3k/akt/mtor pathway , prostate , cell growth , medicine , radiation therapy , cyclin dependent kinase 1 , cancer , cyclin b1 , cell cycle , endocrinology , biology , signal transduction , kinase , microbiology and biotechnology , protein kinase a , genetics
Background Exendin‐4, one of the most widely used antidiabetic drugs, has recently been reported to have potential antitumor effects in cancers. Prostate cancer (PC) is one of the most common cancers in male patients with type 2 diabetes mellitus, and radiotherapy plays a vital role in the therapy of PC. Whether exendin‐4 has the potential to enhance PC response to ionizing radiation (IR) remains unknown. We aimed to explore whether exendin‐4 radiosensitizes PC cells. Methods GLP‐1 receptor (GLP‐1R) expression in PC tissue samples and cell lines were analyzed, Human prostate cancer cells (PC3 and LNCap) were treated with IR and exendin‐4, and subjected to proliferation, clone formation, cell cycle, immunoblotting, and immunohistochemical analysis. An in situ prostate tumor of animal model was established. Results We found that GLP‐1R was expressed in human PC tissues and cell lines. 1‐100 nM exendin‐4 promoted the anti‐proliferation effects of IR in vitro and in vivo, and enhanced radiation‐induced G2/M cycle arrest in PC cells in a dose‐dependent manner. Furthermore, Ex‐4 increased AMPK phosphorylation, decrease the levels of p‐mTOR, cyclin B, and p34 cdc2 . Conclusions Our study suggested exendin‐4 radiosensitizes PC cells via activation of AMPK A and subsequent inhibition of p‐mTOR, cyclin B, and p34cdc2 activation.