title: c-Met inhibition enhances chemosensitivity of human ovarian cancer cells.
abstract: In clinical practice, human ovarian cancer shows considerable resistance to chemotherapy. This study aimed to investigate the role of c-Met in the chemoresistance of ovarian cancer. Ovarian cancer cell line SKOV3 and OVCAR-3 were pretreated with c-Met inhibitor INCB28060, and then treated with paclitaxel. Cell survival, cell cycle and apoptosis were analyzed by MTT assay, flow cytometry analysis and TUNEL assay, respectively. The activation of c-Met signalling was detected by western blot analysis. INCB28060 inhibited the survival of SKOV3 and OVCAR-3 cells and enhanced the chemosensitivity of SKOV3 and OVCAR-3 cells to paclitaxel. INCB28060 inhibited c-Met signalling, caused mitochondrial membrane depolarization and DNA repair, and induced the apoptosis of SKOV3 and OVCAR-3 cells. c-Met plays an important role in mediating the chemoresistance of ovarian cancer. The combination of c-Met inhibitor and chemotherapy is a promising strategy to human ovarian cancer.
authors.affiliation: Department of Gynaecology and Obstetrics, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Gynaecology and Obstetrics, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China.
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Cheng
mesh_terms: D001549:Benzamides / Q000494:pharmacology* / Q000627:therapeutic use; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D007093:Imidazoles; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D017239:Paclitaxel / Q000494:pharmacology / Q000627:therapeutic use; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D014227:Triazines
chemical_list: D001549:Benzamides; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007093:Imidazoles; D014227:Triazines; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; D017239:Paclitaxel; C000613976:capmatinib
keywords: INCB28060; OVCAR-3; SKOV3; c-Met; chemotherapy; ovarian cancer