Yang Meng-Hang, Chang Ke-Jie, Zheng Jin-Cheng, Huang Hai, Sun Guang-Yuan, Zhao Xue-Wei, Li Bing, Xiu Qing-Yu
Department of Respiratory Medicine, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
Department of Thoracic Surgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
Oncol Lett. 2017 Sep;14(3):3103-3109. doi: 10.3892/ol.2017.6518. Epub 2017 Jul 4.
Arsenic trioxide (AsO) exhibits a remarkable effect on leukemia treatment; however, its effect on solid tumors remains poorly explored. The present study demonstrated the inhibitory effect of AsO on lung cancer and explored its possible mechanism. It was observed that AsO significantly inhibited the growth of lung cancer xenografts and tumor angiogenesis . The inhibitory effect of AsO on cell proliferation was more remarkable in vascular endothelial cells than in lung cancer cells. It was also observed that AsO 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 AsO. These findings suggested that anti-angiogenesis may be an underlying mechanism of AsO anticancer activity in lung cancer.
三氧化二砷（AsO）在白血病治疗中显示出显著效果；然而，其对实体瘤的作用仍未得到充分研究。本研究证明了AsO对肺癌的抑制作用并探讨了其可能机制。观察到AsO显著抑制肺癌异种移植瘤的生长和肿瘤血管生成。AsO对细胞增殖的抑制作用在血管内皮细胞中比在肺癌细胞中更显著。还观察到AsO抑制血管内皮细胞的迁移并在基质胶实验中破坏血管管腔形成。此外，一系列参与血管生成多个阶段的关键信号因子，包括基质金属蛋白酶（MMP）-2、MMP-9、血小板衍生生长因子（PDGF）-BB/PDGF受体-β、血管内皮生长因子（VEGF）-A/VEGF受体-2、碱性成纤维细胞生长因子（FGF）/FGF受体-1和Delta样经典Notch配体4/Notch-1，均受AsO调控。这些发现表明抗血管生成可能是AsO在肺癌中抗癌活性的潜在机制。
