摘要
Objective To investigate the effects of sulindac metabolites on proliferation and apoptosis in the human umbilical vein endothelial cell line ECV304 in vitro Methods The proliferation profile of ECV304 was determined by methyl thiazolyl tetrazolium (MTT) method Cell cycle distribution, apoptosis and the ultrastructure of ECV304 were detected by flow cytometry (FCM) and electron microscopy, respectively Results MTT assay showed that the sulfide inhibited the proliferation of ECV304 and its effect was dose dependent; the IC 50 was 200 μmol/L FCM showed that the sulfide changed cell cycle distribution The cell cycle distribution was as follows: G 1 phase (control group 77 74%±1 58%; sulfone group 75 63%±2 12%; sulfide group 46 12%±1 60%); S phase (control group 13 64%±1 22%; sulfone group 16 40±2 30%; sulfide group 27 26%±2 08%); G 2 M phase (control group 8 61%±0 67%; sulfone group 7 98%±0 49%; sulfide group 26 62%±3 54%) The apoptosis rates in the control group, sulfone group and sulfide group were 6 08%±3 39%, 4 81%±2 14% and 51 90%±5 67%, respectively Sulfide reduced the proportion of G 1 phase, increased the proportion of S phase, G 2 M phase and the apoptosis rate significantly ( P <0 01, vs control) In the sulfide treated cells, there were nuclear fragmentation and chromosomal condensation, shrinkage of the cell and loss of contact with neighboring cells Apoptotic bodies were observed Sulfone showed no effect on cell proliferation, cell cycle distribution or cell morphology Conclusions Sulfide can significantly reduce the proliferation of ECV304, change the cell cycle distribution and arrest cells in G 2 M phase where apoptosis may be induced Sulfone has no such effects on this cell line
目的 探讨舒林酸硫化物及砜化物体外对血管内皮细胞增殖及凋亡的影响。方法 MTT法测定舒林酸硫化物及砜化物对人脐静脉内皮细胞增殖的作用 ,流式细胞仪和电镜分别检测其细胞周期、凋亡和超微结构的改变。结果 MTT显示 ,舒林酸硫化物可显著抑制血管内皮细胞的增殖 ,呈剂量依赖效应 ,IC50 为 2 0 0 μmol/L。流式细胞仪检测结果显示 ,舒林酸硫化物可改变血管内皮细胞的周期分布 ,G0 G1期 (对照组 77 74 %± 1 5 8% ,舒林酸砜化物组 75 6 3%± 2 12 % ,舒林酸硫化物组 4 6 12 %± 1 6 0 % ) ,S期 (对照组 13 6 4%± 1 2 2 % ,舒林酸砜化物组16 4 0 %± 2 30 % ,舒林酸硫化物组 2 7 2 6 %± 2 0 8% ) ,G2 M期 (对照组 8 6 1%± 0 6 7% ,舒林酸砜化物组 7 98%± 0 4 9% ,舒林酸硫化物组 2 6 6 2 %± 3 5 4% )。与对照组比较 ,舒林酸硫化物使G0 G1期细胞显著减少 (P <0 0 1) ,S期增加 (P <0 0 1) ,G2 M增加 (P <0 0 1)。舒林酸硫化物使细胞凋亡率增加 (对照组 6 0 8%± 3 39% ,舒林酸砜化物组 4 81%± 2 14 % ,舒林酸硫化物组 5 1 90 %± 5 6 7% ) ,与对照组比较 ,差异有极显著意义 (P <0 0 1)。电镜下舒林酸硫化物组可见细胞核染色质浓缩 ,细胞膜发泡 ,并出现凋亡小体。
