Get your full text copy in PDF
Yinggang Sun, Liyong Sun, Yanxin An, Xin Shen
(Department of General Surgery, Jinan Military General Hospital, Jinan, Shandong, China (mainland))
Med Sci Monit 2015; 21:2316-2321
DOI: 10.12659/MSM.893590
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.
MATERIAL AND 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.
Keywords: Animals, Anilides - therapeutic use, Colorectal Neoplasms - prevention & control, Cytokines - metabolism, Inflammation Mediators - metabolism, Mice, Mice, Inbred BALB C, Neovascularization, Pathologic - prevention & control, Proto-Oncogene Proteins c-met - antagonists & inhibitors, Pyridines - therapeutic use, Signal Transduction, Xenograft Model Antitumor Assays