title: Valsartan inhibits NPC cell line CNE-2 proliferation and invasion and promotes its sensitivity to radiation.
abstract: The objective of this study was to investigate the effects of angiotensin II and valsartan, an angiotensin II type 1 receptor (AT1R) blocker, combined with γ-radiation, on vascular endothelial growth factor (VEGF) expression, radiosensitivity, invasive potential, and proliferation activity of nasopharyngeal carcinoma (CNE-2) in vitro. Reverse-transcription PCR and ELISA assayed VEGF expression and secretion in CNE-2 in vitro. Radiosensitization of valsartan on CNE-2 cell in vitro was investigated by a colony-forming assay. The effect of AT1R blocker combined with radiation on invasive potential of CNE-2 cells was evaluated using 24-well Matrigel invasion chambers (Transwell). The apoptosis-inducing effect of valsartan combined with irradiation on apoptosis of CNE-2 was identified by flow cytometry. AT1R was expressed in nasopharyngeal carcinoma cell lines CNE-1 and CNE-2. The expression and secretion of VEGF in CNE-2 could be induced either by angiotensin II or γ-radiation. Furthermore, the suppression of AT1R activation reduced cellular proliferation, invasive potential and resistance to γ-radiation in nasopharyngeal carcinoma cells. In conclusion, AT1R plays a significant role not only in proliferation and invasion, but also in radiation resistance in nasopharyngeal carcinoma cells, the mechanism of which may be involved in the regulation of VEGF expression and secretion.
authors.affiliation: Cancer Center of the Affiliated Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wujiadun, Wuhan, Hubei, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.forename: Gang
authors.initials: G
authors.lastname: Wu
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects / Q000528:radiation effects; D002465:Cell Movement / Q000187:drug effects / Q000528:radiation effects; D049109:Cell Proliferation / Q000187:drug effects* / Q000528:radiation effects; D003037:Cobalt Radioisotopes; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005720:Gamma Rays; D006801:Humans; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000532:radiotherapy; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000235:genetics; D011836:Radiation Tolerance / Q000187:drug effects*; D060888:Real-Time Polymerase Chain Reaction; D044140:Receptor, Angiotensin, Type 1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013777:Tetrazoles / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D003037:Cobalt Radioisotopes; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000804:Angiotensin II; D000068756:Valsartan; D014633:Valine