Abstract
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.
Highlights
Treatments based on cell death represent an effective way of controlling cancer growth locally, and radiotherapy (RT) represents the most effective postoperative treatment for cervical and head and neck squamous cell carcinoma [1, 2]
We first analyzed platelet-activating factor receptor (PAFR) (PTAFR) expression in two cervical cancer datasets retrieved from GEO web database
We evaluate the expression of PAFR in three cervical carcinoma cell lines (C33, SiHa, and HeLa) and in two squamous carcinoma cell lines (SCC90 and SCC78) compared to an immortalized keratinocyte (HaCaT)
Summary
Treatments based on cell death represent an effective way of controlling cancer growth locally, and radiotherapy (RT) represents the most effective postoperative treatment for cervical and head and neck squamous cell carcinoma [1, 2]. They have an important drawback, which is the possibility of the exacerbated growth of tumor cells that survived treatment (a phenomenon known as tumor repopulation). Apoptosis-induced proliferation is a physiological process that controls cell replacement in healthy or wounded tissue [3]. It was shown that this apoptosis-induced tumor growth was inhibited if mice were pretreated with antagonists of plateletactivating factor receptor (PAFR) [6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
