title: MET inhibitor PHA-665752 suppresses the hepatocyte growth factor-induced cell proliferation and radioresistance in nasopharyngeal carcinoma cells.
abstract: Although ionizing radiation (IR) has provided considerable improvements in nasopharyngeal carcinoma (NPC), in subsets of patients, radioresistance is still a major problem in the treatment. In this study, we demonstrated that irradiation induced MET overexpression and activation, and the aberrant MET signal mediated by hepatocyte growth factor (HGF) induced radioresistance. We also found that MET inhibitor PHA-665752 effectively suppressed HGF induced cell proliferation and radioresistance in NPC cells. Further investigation indicated that PHA-665752 suppressed the phosphorylation of the Akt, ERK1/2, and STAT3 proteins in a dose-dependent manner. Our data indicated that the combination of IR with a MET inhibitor, such as PHA-665752, might be a promising therapeutic strategy for NPC.
authors.affiliation: Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Tongxin
authors.initials: T
authors.lastname: Liu
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Quanquan
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Yuqin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Longhua
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China. Electronic address: wangwei9500@hotmail.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
mesh_terms: D002277:Carcinoma; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D059248:Chemoradiotherapy / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects / Q000528:radiation effects; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D007211:Indoles / Q000008:administration & dosage*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011836:Radiation Tolerance; D013450:Sulfones / Q000008:administration & dosage*; D016896:Treatment Outcome; D015854:Up-Regulation / Q000187:drug effects / Q000528:radiation effects
chemical_list: C480541:5-((2,6-dichlorobenzyl)sulfonyl)-3-((3,5-dimethyl-4-((2-(pyrrolidin-1-ylmethyl)pyrrolidin-1-yl)carbonyl)-1H-pyrrol-2-yl)methylene)-1,3-dihydro-2H-indol-2-one; D007211:Indoles; D013450:Sulfones; D017228:Hepatocyte Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
keywords: MET inhibitor; Nasopharyngeal carcinoma; Radiosensitivity