三氧化二砷抗肝癌血管新生作用

Effect of arsenic trioxide on the anti-angiogenesis of hepatocarcinoma

目的:探讨三氧化二砷(As2O3)注射液抗肝癌血管新生的作用及其相关机制。方法:采用MTT法、透射电镜观察、免疫组化、鸡胚尿囊膜(CAM)血管形成实验等方法,观察As2O3注射液对人肝癌细胞株SMMC-7721和人脐静脉内皮细胞ECV304生长、超微结构、血管内皮生长因子(VEGF)和表皮生长因子受体(EGFR)蛋白表达以及对CAM血管形成的影响。结果:As2O3能显著抑制人肝癌细胞SMMC-7721和人脐静脉内皮细胞ECV304生长,用药后诱导其出现了典型的细胞凋亡超微结构改变;As2O3对SMMC-7721细胞和ECV304细胞VEGF、EGFR的表达均有抑制作用;As2O3能抑制CAM血管形成。结论:As2O3注射液具有显著抗肝癌血管新生作用,其机制与抑制血管内皮细胞生长、诱导血管内皮细胞凋亡、调控肿瘤血管新生相关因子VEGF和EGFR的表达密切相关。

Objective To explore the effects and mechanisms of the anti-angiogenesis of arsenic trioxide（As2O3） injection on hepatocarcinoma. Methods As2O3 ＇ s action on the cell growth, uhrastructure and the expression of vascular endothelial growth factor（VEGF） and epidermal growth factor receptor（EGFR） of human hepatocarcinoma cell line SMMC-7721 and human umbilical vein cell line ECV304 was observed by MTT assay, transmission eleetronmicroseopy detection and immunohistoehemieal staining. The inhibitory effect of As2O3 on angiogenesis was investigated by the method of chick chorioallantoic membrane（CAM）. Results As2O3 could obviously inhibit the growth of SMMC-7721 and ECV304,induce them appearing typical apoptosis ultrastructure changes and down-regulate the expression of VEGF and EGFR. As2O3 could also inhibit the angiogenesis in the CAM. Conclusions As2O3 injection can significantly inhibit tumor angiogenesis, which is closely related to suppressing the growth of vascular endothelial cell,inducing the apoptosis of vascular endothelial cell and down-regulating the expression of VEGF and EGFR.