RhoA在洛伐他汀抑制HepG2细胞增殖中的作用.doc

RhoA在洛伐他汀抑制HepG2细胞增殖中的作用
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作者:吴宝安,梁力建,李威,宋香茹
【关键词】羟甲基戊二酰辅酶A还原酶抑制剂;HepG2细胞;增殖;RhoA
[摘要]目的:探讨RhoA在洛伐他汀抑制HepG2细胞增殖过程中所起的作用。方法:用基因芯片、RT_PCR和Western blot检测洛伐他汀作用前、后HepG2细胞中RhoA的表达。结果:加入洛伐他汀后,mRNA(RhoA)和RhoA蛋白水平均上调;加入香叶基香叶基焦磷酸或法呢基焦磷酸后,RhoA蛋白水平上调被不同程度逆转。结论:减少RhoA香叶酯化,抑制RhoA的细胞膜锚着可能是洛伐他汀抑制HepG2增殖的机制之一。
[关键词]羟甲基戊二酰辅酶A还原酶抑制剂;HepG2细胞;增殖;RhoA
[Abstract]Objective: To study the role of RhoA in lovastatin_inhibited proliferation of HepG2 cells. Methods: The cDNA microarray assay, RT_PCR and Western blot were carried to analyze the mRNA and protein expression of RhoA, respectively. Results: The mRNA and protein expression levels of RhoA were up_regulated in lovastatin_inhibited HepG2 cells. This response could be reversed by addition of geranylgeranyl pyrophosphate or farnesyl pyrophosphate in different degrees. Conclusion: RhoA isoprenylation inhibition and its delocalization from the cell membrane may be one of the mechanisms of lovastatin_inhibited anti_proliferation effect in HepG2 cells.
[Key Words]3_hydroxy_3_methyl glutaryl coenzyme A reductase inhibitor; HepG2 cell; proliferation; RhoA
羟甲基戊二酰辅酶A(HMG_CoA)还原酶抑制剂通称他汀类药物(statins),广泛用于高脂血症的治疗。近年来statins的抗肿瘤作用日益受到重视。洛伐他汀有诱导头颈部鳞癌、甲状腺癌细胞凋亡的作用[1,2]。口服普伐他汀能延长晚期肝细胞癌患者中位生存期[3]。我们发现,洛伐他汀对人肝癌细胞系HepG2细胞的增殖有抑制作用。RhoA(Ras相似物成员A,Ras homolog gene family,member A)属Rho家族蛋白的Rho亚家族成员,可通过多种信号途径参与调节细胞的