Axitinib, a selective inhibitor of vascular endothelial growth factor receptor, exerts an anticancer effect in melanoma through promoting antitumor immunity.
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| Abstract |
In this study, we investigated the antitumor activity of axitinib, a selective inhibitor of vascular endothelial growth factor receptor tyrosine kinases, against melanoma cells. Axitinib dose-dependently inhibited the proliferation and induced the apoptosis of B16F1 cells in vitro. In a mouse model of melanoma xenograft, axitinib significantly suppressed tumor growth and induced apoptosis of cells in tumor tissues at a dose of 25 mg/kg. In addition, axitinib suppressed the lung metastasis of melanoma cells and prolonged the life span of tumor-bearing mice. Axitinib also enhanced the proportion of CD8⁺ T cells and reduced the proportion of myeloid-derived suppressor cells in CD45.2⁺ cells, whereas the proportions of CD4⁺ T cells and Treg cells were not affected. The mRNA expressions of inducible nitric oxide synthases-2 and arginase-1, which were associated with the function of myeloid-derived suppressor cells in tumor tissues, were inhibited by axitinib. Moreover, axitinib suppressed the expressions of proinflammatory cytokines such as IL-6, TNF-α, and IFN-γ. Altogether, our results showed the unique antitumor mechanism of axitinib and provided useful information for its clinical application.
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| Authors | Xiaohua Zhang, Xianying Fang, Zhenzhen Gao, Wei Chen, Feifei Tao, Peifen Cai, Huaqin Yuan, Yongqian Shu, Qiang Xu, Yang Sun, Yanhong Gu |
| Journal | Anti-cancer drugs (Anticancer Drugs) Vol. 25 Issue 2 Pg. 204-11 (Feb 2014) ISSN: 1473-5741 [Electronic] England |
| PMID | 24135499 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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