摘要
为了研究重组人p43(YS-1)蛋白对血管生成的影响及其机制,并考察其对肺癌实体瘤的抑制作用。采用内皮细胞增殖实验、细胞迁移实验、管腔形成实验、大鼠动脉环体外实验、鸡胚尿囊膜体内实验考察YS-1的抗血管生成作用;采用Western印迹法检测细胞内磷酸化MEK1/2、Akt蛋白质的表达;选用人肺腺癌A-549裸小鼠移植瘤模型检测YS-1的体内抗肿瘤活性。结果发现,YS-1能明显抑制内皮细胞迁移和管腔形成,可以抑制体外培养的大鼠动脉环微血管样结构及鸡胚尿囊膜血管,YS-1可以明显抑制血管内皮生长因子(VEGF)诱导的内皮细胞中VEGFR2及下游MEK1/2及Akt的磷酸化,YS-1高剂量(10 mg/kg)能显著抑制肺癌A549移植瘤的生长。研究结果表明:YS-1能抑制人肺腺癌A-549裸鼠移植瘤的生长,其作用机制可能跟抑制VEGF引起的VEGFR2活化及信号转导而影响血管生成有关。
The purpose of this study was to investigate the effects and mechanism of recombinant human p43 (YS-1) on angiogenesis, and explore the antitumor activity of YS-1 in nude mice xenografted with lung adenocar- cinoma A-549. Endothelial cell proliferation assay, cell migration assay, tube formation assay, rat aortic ring assay and chicken chorioallantoic membrane(CAM) assay were used to evaluate the anti-angiogenetic activity of YS-1, and Western blot analysis was used to investigate the related mechanism. A model of lung adenocarcinoma A-549 xenograft in nude mice was used to explore the antitumor efficacy of YS-1. It was found that YS-1 inhibited endo- thelial cell migration and tube formation, and YS-1 obviously inhibited microvessel sprouting from rat aortic rings and the vessel growth in CAM. In addition, YS-1 attenuated the activation of VEGFR2, MEK1/2 and Akt in response to vascular endothelial growth factor (VEGF). Moreover, high dose of YS-1 ( 10 mg/kg) was shown to exert a remarkable antitumor effect in the examined model. Therefore, YS-1 can inhibit adenocarcinoma A-549 xenograft in nude mice and its mechanism may be related to the inhibition of angiogenesis resulting from the attenuation of activated VEGFR2 and downstream signaling molecules.
出处
《中国药科大学学报》
CAS
CSCD
北大核心
2011年第5期467-472,共6页
Journal of China Pharmaceutical University
基金
国家自然科学基金资助项目(No.81071841)~~