三氧化二砷抗肿瘤血管形成研究

Effect of arsenic trioxide on vascularization of tumor

目的:探讨三氧化二砷(As2O3)注射液抗肿瘤血管形成的作用及其相关机制. 方法:采用MTT比色法、鸡胚绒毛尿囊膜(CAM)血管形成实验和免疫组化等方法观察As2O3对内皮细胞株ECV304 增生、CAM血管形成以及对裸鼠肝癌移植瘤LCI-D20表达血管内皮生长因子(VEGF)的影响. 结果:As2O3有显著抑制内皮细胞增生作用;能抑制CAM血管形成,其机制与损伤形成血管的原始间充质细胞、破坏血管形成中的内皮细胞的结构和功能有关;As2O3并能降低裸鼠人肝癌转移模型肝移植瘤VEGF的表达. 结论:As2O3注射液有明显的抗肿瘤血管形成作用,其机制可能与破坏内皮细胞结构和功能、抑制内皮细胞增生以及抑制肿瘤组织表达VEGF有关.

AIM: To explore the effects and mechanisms of anti-vas-cularization of arsenic trioxide (As2O3) injection on the human hepatocellular carcinoma (HCC) cells. METHODS: Human umbilical vein cell line ECV304 and the nude mice with the high metastastic human HCC transplanted in situ LCI-D20 were used. The growth of ECV304 was analyzed by MTT assay. The inhibitory effect of As203 on tumor neo-vascularization was investigated by the method of chick chorioallantoic membrane (CAM). The changes of VEGF's expression in the transplanted HCC tissue were investigated by using immunohistochemical SP staining. RESULTS: As2O3 could inhibit the growth of ECV304 cell line, and down-regulate VEGF's expression. As2O3 could also inhibit the vascularization in the CAM, and electron microscopy showed that As2O3 could damage primitive mes-enchymal cells and vascular endothelial cells, and inhibite neovascular gemmation. The expression of VEGF was down-regulated in vivo studies. CONCLUSION: As2O3 injection can inhibit the tumor neovascularization by supressing the growth of vascular endothelial cell, down-regulating the expression of VEGF, damaging the primitive mesenchymal cells and inhibiting neovascular fromation.