title: Axitinib, a selective inhibitor of vascular endothelial growth factor receptor, exerts an anticancer effect in melanoma through promoting antitumor immunity.
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.
authors.affiliation: aDepartment of Clinical Oncology, The First Affiliated Hospital with Nanjing Medical University bState Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Zhang
authors.forename: Xianying
authors.initials: X
authors.lastname: Fang
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Gao
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Feifei
authors.initials: F
authors.lastname: Tao
authors.forename: Peifen
authors.initials: P
authors.lastname: Cai
authors.forename: Huaqin
authors.initials: H
authors.lastname: Yuan
authors.forename: Yongqian
authors.initials: Y
authors.lastname: Shu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xu
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Gu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D000077784:Axitinib; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007191:Indazoles / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D059016:Tumor Microenvironment / Q000187:drug effects / Q000276:immunology; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000037:antagonists & inhibitors* / Q000502:physiology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D007191:Indazoles; D000077784:Axitinib; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1