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沙利度胺是一种抗血管生成药物,临床上用于治疗多种肿瘤,但其抗肿瘤血管生成机制尚不十分清楚.本文采用MTT法观察沙利度胺对体外培养的血管内皮细胞增殖的影响.结果发现,沙利度胺能够抑制血管内皮细胞的增殖,其IC50为16.47μg/mL;然后采用Hoechst染色和流式细胞仪检测细胞凋亡和细胞周期,发现沙利度胺能够诱导内皮细胞凋亡,并干扰细胞的周期,出现G0/G1期阻滞.最后,通过Western印迹方法分析沙利度胺对血管内皮细胞Bcl-2蛋白表达的影响,发现抗凋亡的Bcl-2蛋白表达水平随沙利度胺浓度增大而降低.初步结果提示,沙利度胺可能通过阻遏抗凋亡分子Bcl-2表达,激活诱导G1期阻滞的信号通路而抑制内皮细胞新生,从而抑制肿瘤生长.诱导内皮细胞凋亡及G1期阻滞的具体分子机制正在研究中.
Thalidomide is an anti-angiogenic drug that is clinically used to treat a variety of tumors, but its antitumor angiogenesis mechanism is not yet fully understood.In this paper, MTT assay was used to observe the effects of thalidomide on the proliferation of cultured vascular endothelial cells Thalidomide could inhibit the proliferation of vascular endothelial cells with the IC50 of 16.47μg / mL. Then, the apoptosis and cell cycle were detected by Hoechst staining and flow cytometry, and thalidomide was found to induce Endothelial cell apoptosis and interference with the cell cycle, the G0 / G1 phase arrest.Finally, the influence of thalidomide on Bcl-2 protein expression in vascular endothelial cells was analyzed by Western blotting and found that anti-apoptotic Bcl-2 The level of thalidomide decreased.Preliminary results suggest that thalidomide can inhibit endothelial cell regeneration by inhibiting the expression of anti-apoptotic molecule Bcl-2 and activating the signaling pathway of G1 phase arrest Inhibition of tumor growth.Induced endothelial cell apoptosis and G1 phase arrest specific molecular mechanisms are under study.