title: Famitinib enhances nasopharyngeal cancer cell radiosensitivity by attenuating radiation-induced phosphorylation of platelet-derived growth factor receptor and c-kit and inhibiting microvessel formation.
abstract: OBJECTIVE
  Famitinib is a novel tyrosine kinase inhibitor. We investigated the effects of famitinib on the radiosensitivity of human nasopharyngeal carcinoma (NPC) cell radiosensitivity in vitro and in vivo, and explored its possible mechanisms.
  
  
  METHODS
  Human nasopharyngeal carcinoma cell line (CNE-2) were treated with famitinib and radiation, and analyzed by3-(4,5-dimethylthaizol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), clonogenic survival assay, and Western blot. A xenograft model using CNE-2 cells was established to analyze the effects of famitinib and radiation on tumor volume and microvessel density (MVD).
  
  
  RESULTS
  Famitinib dose-dependently inhibited CNE-2 cells growth and significantly reduced clonogenic survival (p < 0.05), with a sensitivity enhancement ratio (SER) of 1.45. The tumor inhibition rate of the combined treatment group was 91%, which was significantly higher than the radiation group (35%, p < 0.05) and famitinib group (46%, p < 0.05). Famitinib attenuated radiation-induced phosphorylation of the platelet-derived growth factor receptor (PDGFR) and stem cell factor (c-kit) at 0, 30, 60 min after radiation treatment. Furthermore, radiation combined with famitinib decreased tumor MVD (p < 0.05).
  
  
  CONCLUSIONS
  Famitinib significantly increased CNE-2 cell radiosensitivity in vitro and in vivo by attenuating radiation-induced PDGFR and c-kit phosphorylation and by inhibiting microvessel formation.
authors.affiliation: a Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China.|b Department of Medical Oncology , Affiliated Cancer Hospital of Zhengzhou University , Zhengzhou , Henan, China.
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Mu
authors.affiliation: a Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China.
authors.forename: Jia
authors.initials: J
authors.lastname: Ma
authors.affiliation: a Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China.
authors.forename: Zhanjie
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: a Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Zhou
authors.affiliation: a Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China.
authors.forename: Shuangbing
authors.initials: S
authors.lastname: Xu
authors.affiliation: a Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China.
authors.forename: You
authors.initials: Y
authors.lastname: Qin
authors.affiliation: a Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China.
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.affiliation: a Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China.
authors.forename: Kunyu
authors.initials: K
authors.lastname: Yang
authors.affiliation: a Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wu
mesh_terms: D000818:Animals; D002277:Carcinoma; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D055806:Microvessels / Q000187:drug effects / Q000473:pathology; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy*; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism* / Q000528:radiation effects; D011758:Pyrroles / Q000494:pharmacology*; D011836:Radiation Tolerance / Q000187:drug effects*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism* / Q000528:radiation effects; D014410:Tumor Stem Cell Assay; D023041:Xenograft Model Antitumor Assays
chemical_list: D007211:Indoles; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; C584390:famitinib; D019009:Proto-Oncogene Proteins c-kit; D020797:Receptor, Platelet-Derived Growth Factor beta
keywords: Famitinib; MVD; PDGFR; c-kit; nasopharyngeal cancer; radiosensitivity