血管抑素与顺铂及健择联用对人血管内皮细胞增殖和凋亡相关蛋白表达的影响

Effects of angiostatin,cisplatin and gemcitabine on proliferation of the vascular endothelial cells and its expression of apoptosis related protein

目的 探讨血管抑素与顺铂及健择联用对内皮细胞增殖的抑制作用及其机制。方法 采用四氮唑喃比色法试验、免疫组织化学染色与电子显微镜等方法检测血管抑素与顺铂及健择治疗后内皮细胞增殖、凋亡及其相关蛋白表达的变化。结果 血管抑素与顺铂及健择明显减少每孔中存活的内皮细胞数 ,并能增加P5 3蛋白表达 ,抑制Bcl 2表达。顺铂和健择抑制内皮细胞的起效剂量明显低于抑制A5 4 9细胞所需的剂量 ,并与血管抑素具有协同作用。血管抑素和顺铂对内皮细胞增殖抑制作用在停止接触 10d后恢复 ,而健择引起的内皮细胞增殖抑制是不可恢复的。结论 血管抑素与顺铂及健择联用可通过抑制内皮细胞增殖 ,而发挥抗血管生成作用。

Objective To investigate the effects of combined angiostatin,cisplatin(DDP) and gemcitabine(GEM) on proliferation of the vascular endothelial cells and their mechanisms.Methods Effects on proliferation,apoptosis and apoptosis-associated protein expression of the human vascular endothelial cells treated by angiostatin,DDP and GEM were evaluated with the methods of MTT,immunohistochemistry,and electric microscopy.Results Angiostatin,DDP and GEM significantly suppressed the proliferation of the endothelial cells,upregulated p53 protein expression and downregulated Bcl-2 expression.Effective doses of DDP and GEM to suppress the endothelial cells were significantly less than those for them to suppress A549 cells.The two cytotoxic drugs had synergic effects with angiostatin.Suppressive effects of angiostatin and DDP disappeared l0 days after stopping exposure to the drugs but suppressive effects of GEM did not recover.Conclusion Angiostatin,cisplatin and gemcitabine may suppress angiostatin through their inhibitory effect on endothelial proliferation.