PAFR selectively mediates radioresistance and irradiation-induced autophagy suppression in prostate cancer cells

// Bing Yao 1, * , Bingqian Liu 1, * , Lei Shi 1, * , Xiang Li 2 , Chuanchuan Ren 1 , Mingbo Cai 3 , Wen Wang 3 , Jianhua Li 1 , Yongde Sun 1 , Yudong Wu 1 , Jianguo Wen 1 1 Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China 2 Department of Plastic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China 3 Department of Gynaecology and Obstetrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China * These authors contributed equally to this work Correspondence to: Yudong Wu, email: yudongwu_zhd@163.com Jianguo Wen, email: wenjg_zhdu@163.com Keywords: platelet activating factor receptor, prostatic neoplasms, radiotherapy, autophagy, drug sensitivity Received: July 22, 2016      Accepted: January 03, 2017      Published: January 14, 2017 ABSTRACT Platelet-activating factor receptor (PAFR) promotes tumorigenesis, angiogenesis and metastasis. Here, we defined the PAFR as a yielding new inhibiting target to selectively enhance the sensitivity of prostate cancer (PCa) cells to radiation. The selective responding to PAFR inhibiter may be caused by the differential expression pattern of PAFR in PCa cells. In this study, we also determined PAFR as a molecular basis by which the radiation induces autophagy suppression independent of activating mTOR pathway. PAFR can bind to the autophagy-indispensable protein Beclin 1, leading to the disability in its serine phosphorylation. The PAFR antagonist Ginkgolide B (GB) can sensitize radiotherapy by disrupting the formation of PAFR/Beclin 1 complex in PC3 and LNCaP cells, which have elevated PAFR expression after radiation exposure. Most importantly, GB efficiently radiosensitized PC3 and LNCaP tumor xenografts in vivo , and significantly reduced tumor burden. Overall, our results elucidated a significant role of GB in selectively improving the outcomes of PCa receiving radiation therapy.