title: PAFR selectively mediates radioresistance and irradiation-induced autophagy suppression in prostate cancer cells.
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.
authors.affiliation: Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Yao
authors.affiliation: Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Bingqian
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Plastic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Chuanchuan
authors.initials: C
authors.lastname: Ren
authors.affiliation: Department of Gynaecology and Obstetrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Mingbo
authors.initials: M
authors.lastname: Cai
authors.affiliation: Department of Gynaecology and Obstetrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Yongde
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Yudong
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Wen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D015153:Blotting, Western; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D046934:Ginkgolides / Q000494:pharmacology*; D006801:Humans; D047468:Immunoprecipitation; D007783:Lactones / Q000494:pharmacology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011471:Prostatic Neoplasms / Q000473:pathology*; D011836:Radiation Tolerance / Q000502:physiology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D046934:Ginkgolides; D007783:Lactones; D010980:Platelet Membrane Glycoproteins; D011838:Radiation-Sensitizing Agents; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; C045856:ginkgolide B
keywords: autophagy; drug sensitivity; platelet activating factor receptor; prostatic neoplasms; radiotherapy