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08 August 2015 : Animal Research  

Cabozantinib, a Novel c-Met Inhibitor, Inhibits Colorectal Cancer Development in a Xenograft Model

Yinggang SunABC, Liyong SunBC, Yanxin AnDE, Xin ShenFG

DOI: 10.12659/MSM.893590

Med Sci Monit 2015; 21:2316-2321

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.

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: Anilides - therapeutic use, Colorectal Neoplasms - prevention & control, Cytokines - metabolism, Inflammation Mediators - metabolism, Mice, Inbred BALB C, Neovascularization, Pathologic - prevention & control, Proto-Oncogene Proteins c-met - antagonists & inhibitors, Pyridines - therapeutic use, Signal Transduction, Xenograft Model Antitumor Assays

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Medical Science Monitor Basic Research eISSN: 2325-4416
Medical Science Monitor Basic Research eISSN: 2325-4416