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

Yao, Bing; Liu, Bingqian; Shi, Lei; Li, Xiang; Ren, Chuanchuan; Cai, Mingbo; Wang, Wen; Li, Jianhua; Sun, Yongde; Wu, Yue; Wen, Jie

doi:10.18632/oncotarget.14647

Cited by 19 publications

(14 citation statements)

References 35 publications

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“…The association of PAFR antagonists with chemotherapy agents leads to increased tumor cell death and improved treatment effectiveness ( 14 , 37 – 39 ). We have recently found similar effects with the association of PAFR antagonists and RT ( 7 , 13 , 40 ). The present study provides additional support for the functional significance of the PAF/PAFR system in tumor RT.…”

Section: Discussionsupporting

confidence: 68%

Platelet-Activating Factor Receptor Ligands Protect Tumor Cells from Radiation-Induced Cell Death

et al. 2018

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Irradiation generates oxidized phospholipids that activate platelet-activating factor receptor (PAFR) associated with pro-tumorigenic effects. Here, we investigated the involvement of PAFR in tumor cell survival after irradiation. Cervical cancer samples presented higher levels of PAF-receptor gene (PTAFR) when compared with normal cervical tissue. In cervical cancer patients submitted to radiotherapy (RT), the expression of PTAFR was significantly increased. Cervical cancer-derived cell lines (C33, SiHa, and HeLa) and squamous carcinoma cell lines (SCC90 and SCC78) express higher levels of PAFR mRNA and protein than immortalized keratinocytes. Gamma radiation increased PAFR expression and induced PAFR ligands and prostaglandin E2 (PGE2) in these tumor cells. The blocking of PAFR with the antagonist CV3938 before irradiation inhibited PGE2 and increased tumor cells death. Similarly, human carcinoma cells transfected with PAFR (KBP) were more resistant to radiation compared to those lacking the receptor (KBM). PGE2 production by irradiated KBP cells was also inhibited by CV3988. These results show that irradiation of carcinoma cells generates PAFR ligands that protect tumor cells from death and suggests that the combination of RT with a PAFR antagonist could be a promising strategy for cancer treatment.

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Section: Discussionsupporting

confidence: 68%

Platelet-Activating Factor Receptor Ligands Protect Tumor Cells from Radiation-Induced Cell Death

et al. 2018

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“…In prostate cancer, PAFR was overexpressed in response to irradiation, and the PAFR antagonist ginkgolide B reduced cell viability. The radiosensitizing effect of this antagonist was observed in xenograft tumors, and this effect was shown to be mediated by the interaction between PAFR and beclin-1, leading to inactivation of autophagy 8 .…”

Section: Pafr and Tumor Repopulation After Chemo- And Radiotherapymentioning

confidence: 99%

“…PAF production relies on inflammatory stimuli or stress, such as that induced by radiotherapy and chemotherapy 5 - 10 . However, under physiologic conditions, a small and continuous amount of PAF is generated from cell membrane phospholipids by de novo synthesis, which is responsible for the functional regulation of plasma membranes 11 , 12 .…”

Section: Introductionmentioning

confidence: 99%

Platelet activating factor receptor antagonists improve the efficacy of experimental chemo- and radiotherapy

Silva¹,

Andrade²,

Jancar³

et al. 2018

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Platelet activating factor is a lipid mediator of inflammation, and in recent decades, it has emerged as an important factor in tumor outcomes. Platelet activating factor acts by specific binding to its receptor, which is present in both tumor cells and cells that infiltrate tumors. Pro-tumorigenic effects of platelet activating factor receptor in tumors includes promotion of tumor cell proliferation, production of survival signals, migration of vascular cells and formation of new vessels and stimulation of dendritic cells and macrophages suppressor phenotype. In experimental models, blocking of platelet activating factor receptor reduced tumor growth and increased animal survival. During chemotherapy and radiotherapy, tumor cells that survive treatment undergo accelerated proliferation, a phenomenon known as tumor cell repopulation. Work from our group and others showed that these treatments induce overproduction of platelet activating factor-like molecules and increase expression of its receptor in tumor cells. In this scenario, antagonists of platelet activating factor markedly reduced tumor repopulation. Here, we note that combining chemo- and radiotherapy with platelet activating factor antagonists could be a promising strategy for cancer treatment.

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“…Consequently, this suggests that some anti‐inflammatory drugs such as non‐steroidal anti‐inflammatory drugs (NSAIDs) and PAFr antagonists could be used to treat certain types of cancer . In addition, the PAFr has been implicated in modulating radiation and cisplatin sensitivity in various cancers, including prostate, cervical, and ovarian cancers …”

Section: Inflammatory Diseasesmentioning

confidence: 99%

Progress in the Development of Platelet‐Activating Factor Receptor (PAFr) Antagonists and Applications in the Treatment of Inflammatory Diseases

et al. 2018

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Platelet-activating factor (PAF) and its receptor (PAFr) have been implicated in a wide range of diseases and disorders that originate from the activation of inflammatory pathways. Although the exact structure of the binding site on the PAFr remains unknown, the PAFr is a well-established therapeutic target, and an array of structurally diverse PAFr antagonists have been identified. These include compounds that are structurally similar to the natural PAF ligand, synthetic heterocycles, complex polycyclic natural products, and various metal complexes. This review provides an update on more than 20 years of progress in this area. The development and synthesis of new PAFr antagonists, structure-activity relationship studies, the biological activity of these molecules, and their therapeutic potential are discussed.

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

Cited by 19 publications

References 35 publications

Platelet-Activating Factor Receptor Ligands Protect Tumor Cells from Radiation-Induced Cell Death

Platelet-Activating Factor Receptor Ligands Protect Tumor Cells from Radiation-Induced Cell Death

Platelet activating factor receptor antagonists improve the efficacy of experimental chemo- and radiotherapy

Progress in the Development of Platelet‐Activating Factor Receptor (PAFr) Antagonists and Applications in the Treatment of Inflammatory Diseases

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