title: Cabozantinib, a Novel c-Met Inhibitor, Inhibits Colorectal Cancer Development in a Xenograft Model.
abstract: BACKGROUND
  Angiogenesis plays a critical role during tumor development. c-Met has recently been implicated in the angiogenesis of various tumors, leaving its role in colorectal cancer (CRC) unknown. In this study, we aimed to evaluate the effect of a novel c-Met inhibitor, cabozantinib, on the tumor growth and angiogenesis in a CRC mouse model.
  
  
  METHODS
  A mouse CRC xenograft model was used to evaluate the effect of cabozantinib on vivo growth of tumors and angiogenesis. The expression of angiogenesis-related factors was evaluated by immunohistochemistry (IHC) and Western blotting. Levels of serum cytokines were detected by ELISA.
  
  
  RESULTS
  Cabozantinib effectively reduced tumor size and angiogenesis, and suppressed the expression of vascular endothelial growth factor (VEGF) in tumor tissues, possibly via the inhibition of Sonic Hedgehog (SHH) pathway.
  
  
  CONCLUSIONS
  The blockade of c-Met inhibits the tumor growth and angiogenesis via modulating SHH pathway, suggesting a potential strategy in the treatment of CRC.
authors.affiliation: Department of General Surgery, Jinan Military General Hospital, Jinan, Shandong, China (mainland).
authors.forename: Yinggang
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of General Surgery, Jinan Military General Hospital, Jinan, Shandong, China (mainland).
authors.forename: Liyong
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of General Surgery, Jinan Military General Hospital, Jinan, Shandong, China (mainland).
authors.forename: Yanxin
authors.initials: Y
authors.lastname: An
authors.affiliation: Department of General Surgery, Jinan Military General Hospital, Jinan, Shandong, China (mainland).
authors.forename: Xin
authors.initials: X
authors.lastname: Shen
mesh_terms: D000813:Anilides / Q000627:therapeutic use*; D000818:Animals; D015179:Colorectal Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000627:therapeutic use*; D015398:Signal Transduction; D023041:Xenograft Model Antitumor Assays
chemical_list: D000813:Anilides; D016207:Cytokines; D018836:Inflammation Mediators; D011725:Pyridines; C558660:cabozantinib; D019859:Proto-Oncogene Proteins c-met