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

卡博替尼是一种新型c-Met抑制剂,可在异种移植模型中抑制结直肠癌的发展。

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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.

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