HMG-CoA还原酶抑制剂对胃癌细胞增殖的影响

Effects of HMG-CoA Reductase Inhibitors on Proliferation and Growth of Gastric Cancer Cells in Vitro

目的:研究3羟基3甲基戊二烯辅酶A3hydroxy3methylgutarylcoenzymeAHMGCoA还原酶抑制剂对胃癌细胞增殖的影响。方法:采用MTT比色法和流式细胞仪检测胃癌细胞的增殖活性和细胞周期。结果:辛伐他丁可明显降低MNK450胃癌细胞增殖活性、S期细胞比和细胞增殖指数,在浓度大于1μmol/L时,与对照组比较具有显著性差异(P<0.05)。0.2～100μmol/L5种浓度辛伐他丁作用72h后,胃癌细胞增殖抑制率分别为8.0%、18.0%、30.7%、42.6%和51.5%,同时加入10mmol/L甲羟戊酸则可逆转辛伐他丁的抑制作用。1～20μmol/L3种浓度辛伐他丁可阻止胃癌细胞由G1期进入S期;20μmol/L辛伐他丁作用36h后,胃癌细胞S期细胞比从32.1%下降至15.0%,加入10mmol/L甲羟戊酸则可逆转5μmol/L辛伐他丁对胃癌细胞周期的影响。而普伐他丁对胃癌细胞增殖活性无明显影响(P>0.05)。结论:脂溶性HMGCoA还原酶抑制剂辛伐他丁可抑制胃癌细胞生长增殖,提示辛伐他丁具有抗肿瘤特性。

Objective:This study was designed to investigate the effects of HMG-CoA reductase i nhibitors on proliferation and growth of gastric cancer cells.Methods :MTT colorimetric assay and flow cyto metry were used to measure the proliferative activity and the cell cycle progression of gastric cancer MNK 450 cells.Results:Gastric cancer cells treated with Simvastatin had reductions in proliferative activity,S-phase fractio n and proliferative index in a dose dependent manner with statistical significance at the con centrations of more than 1μmol /L as compared with normal contro l.The inhibitory rate ranged from 8.0%to 51.5%when cells were tre ated with Simvastatin at the concent rations of 0.2-100μmol /L for 72hours.Inhibition induced by Simvastatin was reversed by simultaneous additio n of mevalonic acid at the concentati on of 10mmol /L.Gastric cancer cells were arrested b y Simvastafin in G 1 at the concentations of 1-20μmol /L.The fraction of S-phase cells was reduced from 32.1%to 15.0%after exp osure to 20μmol /L Simvastatin for 36hours.The a ddition of 10mmol /L mevalonic acid overcome G 1 arrest induced by 5μmol /L Simvastatin.Otherwise,the p ercentage of cells in G 2 plus M 2 remained rather constant throughou t the treatment.Meanwhile,Pravastatin had no significant effect on the proliferatiive activity of gastric cancer MNK 450 cells.Conclusion:Simvastatin could inhibit the proliferation and growth of gastric cancer cells,which suggests that Simvastatin has the effect of antitumor.