血管紧张素抑制剂对宫颈癌HeLa细胞的AT1R,MMP2和MMP9表达的影响

Influence of Angiotensin Inhibitor on the Expression of Cervical Cancer HeLa Cells AT1R, MMP2 and MMP9

目的:探讨血管紧张素转化酶抑制剂(ACEI)卡托普利及血管紧张素Ⅱ1型受体抑制剂(ARB)缬沙坦对血管紧张素Ⅱ(AngⅡ)诱导的宫颈癌HeLa细胞株的血管紧张素Ⅱ1型受体(AT1R)抗原、基质金属蛋白酶2(MMP2)、MMP9蛋白和基因表达的影响。方法:宫颈癌HeLa细胞株单独使用AngⅡ、联合卡托普利或缬沙坦,细胞生长状态测定法(噻唑蓝比色试验法)检测细胞增殖状况,免疫荧光细胞化学法测定AT1R、MMP2和MMP9蛋白表达水平,实时荧光反转录聚合酶链反应(Real-TimeRT-PCR)法检测AT1R、MMP2、MMP9基因的相对表达。结果:MTT法测定结果显示,AngⅡ并无明显的促进细胞增殖的作用,但卡托普利和缬沙坦可抑制AngⅡ作用的宫颈癌HeLa细胞的增殖;免疫荧光细胞化学和Real-TimeRT-PCR的结果则表明,AngⅡ可明显增加AT1R、MMP2和MMP9蛋白和基因的表达,而卡托普利和缬沙坦可抑制其作用。结论:AngⅡ通过AT1R促进宫颈癌HeLa细胞的MMP2和MMP9蛋白和基因的表达,AngⅡ抑制剂卡托普利和缬沙坦可有效抑制其表达。AngⅡ抑制剂有可能成为一种新的抑制宫颈癌转移和延长宫颈癌患者生存期的药物。

Objective： To study the effect of Angiotensin Ⅱ inhibitors,which is angiotensin converting enzyme inhibitor（ACEI）captopril and Ang Ⅱ 1 receptor inhibitor（ARB）valsartan on Ang Ⅱ-induced cervical cancer cell line HeLa AT1R,MMP2,MMP9 protein and gene expression. Methods：Treating cervical cancer HeLa cells alone with Ang Ⅱ,or combined ACEI or ARB. The MTT cell proliferation was detected by immunofluorescence staining method to detect AT1R,MMP2,MMP9 protein levels,Real-Time RT-PCR method of detection AT1R,MMP2,MMP9 gene relative expression. Results：MTT results showed that Ang Ⅱ had no significant role in promoting cell proliferation,but the ACEI and ARB could inhibit the effect of Ang Ⅱ cervical cancer HeLa cells;immunocytochemistry and Real-Time RT-PCR results showed Ang Ⅱ could significantly increase protein and gene expression of AT1R and MMP2 and MMP9,while ACEI and ARB could inhibit the role of Ang Ⅱ. Conclusions：Ang Ⅱcould promote cervical cancer HeLa cells AT1R,MMP2,MMP9 protein and gene expression,which expression could be Ang Ⅱ inhibitors captopril and valsartan inhibited,Ang Ⅱ inhibitors may be a kind of new control of cervical cancer metastasis and prolong survival in patients with cervical cancer drug.