蛋白激酶C抑制剂Staurosporine对人胃癌细胞周期的影响

Effect of Staurosporine on Cell Cycle of Human Gastric Cancer Cells

背景与目的:蛋白激酶C(proteinkinaseC,PKC)已成为一个潜在的有价值的抗肿瘤治疗靶点。本研究旨在探讨PKC抑制剂Staurosporine(ST)对人胃癌细胞株MGC-803和SGC-7901的增殖抑制、凋亡诱导及对其细胞周期的影响。方法:在用台盼蓝拒染法检测细胞增殖抑制率的基础上,通过细胞形态学观察凋亡小体,流式细胞仪检测细胞凋亡率及细胞周期变化。结果:ST抑制MGC-803细胞生长,24h的IC50为54ng/ml,48h的IC50为23ng/ml;ST抑制SGC-7901细胞的生长,24h的IC50为61ng/ml,48h的IC50为37ng/ml。40、60、100ng/mlST分别作用MGC-803细胞24h后,发现G0/G1期细胞分别为(23.6±1.8)%、(11.6±0.7)%、(3.3±0.2)%,而对照组为(54.3±3.1)%;G2/M期细胞分别为(22.6±4.0)%、(35.5±0.4)%、(36.8±5.5)%,而对照组为(13.5±0.2)%。40、60、100ng/mlST分别作用于SGC-7901细胞24h后,G0/G1期细胞分别为(27.1±1.4)%、(17.0±3.4)%,(13.7±0.7)%,而对照组为(52.5±4.4)%;G2/M期细胞分别为(21.9±2.6)%、(39.5±4.9)%、(38.4±3.1)%,而对照组为(13.5±2.2)%。实验组细胞与对照组比较,ST使两种细胞G0/G1期明显减少及G2/M期明显增加(P<0.01)。200ng/mlST作用24h后两种细胞的G1期前均出现明显的凋亡峰,可诱导细胞出现典型凋亡小体。

BACKGROUND &OBJECTIVE:Protein kinase C (PKC)has been considered to be a potentially s uitable targ et for anticancer thera py.This study was desig ned to investig ate th e effect of PKC inhibitor staurospor ine(ST)on the inhibition of proliferation,the induction of apoptosis,and the c hang e of cell cycle in human g astric cancer ce ll lines MGC-803and SGC-7901.METHODS :The inhibition rates of cell prolife ration were evaluated by trypan blue exclusion.The apoptotic bodies wer e observed under lig ht microscope and electron microscope.The apoptotic peaks of the cells and the chang es of c ell cycle were analyzed using flow cytom etry.RESULTS :ST inhibited cell g rowth of MGC-803,IC 50 of 24hours was 54ng /ml and IC 50 of 48hours was 23ng /ml.ST inhibited cell g rowth of SGC-7901,IC 50 of 24hours was 61ng /ml and IC 50 of 48hours was 37ng /ml.MGC-803cells were treated by ST at the concentratio ns of 40,60,and 100ng /ml for 24hours,t he percentag es of G 0 /G 1 phag e were23.6±1.8%,11.6±0.7%,and 3.3±0.2%,respectively(54.3±3.1%in control g roup);the percentag es of G 2 /M phag e were 22.6±4.0%,35.5±0.4%,and 36.8±5.5%,respectively(13.5±0.2in control g roup).SGC-7901cells were treated by ST at the concentrations of 40,60,and 100ng /ml for 24hours,the percentag es of G 0 /G 1 phag e were 27.1±1.4%,17.0±3.4%,13.7±0.7%,respectively(52.5±4.4%in control g roup);the percentag es of G 2 /M were 21.9±2.6%,39.5±4.9%,and 38.4±3.1%,respectively(13.5±2.2%in control roup).Compared with the control g roup,th e percentag es of G 0 /G 1 phag e of two cell lines decreased and that of G 2 /M cells increased sig nificantly in the ST tr eated g roup(P <0.01).Treated by ST at the concentration of 200ng /ml,the apop totic peaks and typical apoptotic bo dies were observed.CONCLUSION:ST sig nificantly inhibits the proli feration and induces apoptosis of MGC-803cells a nd SGC-7901cells ;ST induces G 2 /M phase arrest.