Anti-angiogenic effect of arsenic trioxide in lung cancer via inhibition of endothelial cell migration, proliferation and tube formation.
Anti-angiogenic effect of arsenic trioxide in lung cancer via inhibition of endothelial cell migration, proliferation and tube formation.
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DOI：
10.3892/ol.2017.6518
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发表时间：
2017-09
期刊：
影响因子：
2.9
通讯作者：
Meng-hang Yang;Ke-Jie Chang;Jin-Cheng Zheng;Hai Huang;G. Sun;Xuewei Zhao;Bing Li;Q. Xiu
中科院分区：
文献类型：
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作者：
Meng-hang Yang;Ke-Jie Chang;Jin-Cheng Zheng;Hai Huang;G. Sun;Xuewei Zhao;Bing Li;Q. Xiu
三氧化二砷(As_2O_3)在治疗白血病方面显示出显著的效果，但其对实体瘤的作用尚不清楚。本研究证实了三氧化二砷对肺癌的抑制作用，并探讨了其可能的作用机制。结果表明，As_2O_3能显著抑制肺癌移植瘤的生长和体内肿瘤血管生成。As_2O_3在体外对血管内皮细胞的抑制作用比对肺癌细胞的抑制作用更明显。Matrigel实验还观察到As_2O_3抑制血管内皮细胞的迁移，破坏血管内皮细胞的形成。此外，基质金属蛋白酶-2、基质金属蛋白酶-9、血小板衍生生长因子-BB/血小板衍生生长因子受体-β、血管内皮生长因子-A/血管内皮生长因子受体-2、碱性成纤维细胞生长因子/成纤维细胞生长因子受体-1、三角样典型Notch配体4/Notch-1等一系列涉及血管生成多个阶段的关键信号因子也受到As2O_3的调节。这些结果提示，抗血管生成可能是三氧化二砷抗肺癌作用的机制之一。
Arsenic trioxide (As2O3) exhibits a remarkable effect on leukemia treatment; however, its effect on solid tumors remains poorly explored. The present study demonstrated the inhibitory effect of As2O3 on lung cancer and explored its possible mechanism. It was observed that As2O3 significantly inhibited the growth of lung cancer xenografts and tumor angiogenesis in vivo. The inhibitory effect of As2O3 on cell proliferation in vitro was more remarkable in vascular endothelial cells than in lung cancer cells. It was also observed that As2O3 inhibited the migration of vascular endothelial cells and disrupted vascular tube formation on Matrigel assays. In addition, a series of key signaling factors involved in multiple stages of angiogenesis, including matrix metalloproteinase (MMP)-2, MMP-9, platelet-derived growth factor (PDGF)-BB/PDGF receptor-β, vascular endothelial growth factor (VEGF)-A/VEGF receptor-2, basic fibroblast growth factor (FGF)/FGF receptor-1 and delta like canonical Notch ligand 4/Notch-1, were regulated by As2O3. These findings suggested that anti-angiogenesis may be an underlying mechanism of As2O3 anticancer activity in lung cancer.