白藜芦醇对宫颈癌HeLa细胞基质金属蛋白酶及其组织抑制剂的影响  

Effects of resveratrol on the expressions of matrix metalloproteinase and tissue inhibitors of metalloproteinase in cervical cancer HeLa cells

作　　者：董德刚[1] 郭恩绵[1] 张瑶[2] 鲁艳明[2] 张淑兰[2] 

机构地区：[1]辽宁中医药大学第一附属医院妇产科,辽宁沈阳110032 [2]中国医科大学附属盛京医院妇产科,辽宁沈阳110004

出　　处：《中华肿瘤防治杂志》2007年第7期489-493,共5页Chinese Journal of Cancer Prevention and Treatment

基　　金：国家自然科学基金(30571959)

摘　　要：目的探讨白藜芦醇对宫颈癌侵袭和转移的影响及其初步作用机制。方法选用Transwell侵袭系统,观察白藜芦醇对宫颈癌细胞侵袭转移的影响;用明胶酶谱法、RT-PCR和Western blot法了解白藜芦醇对宫颈癌细胞MMP-2、MMP-9、TIMP-1、TIMP-2的活性、mRNA及蛋白表达的影响。结果白藜芦醇1、0.5mmol/L两组平均穿过的细胞数分别为9.20±1.924,10.20±2.049与空白对照组(39.80±2.387)相比,明显减少,P<0.05。同时,白藜芦醇能够明显降低宫颈癌细胞MMP-2、MMP-9的活性、mRNA及蛋白表达水平(P<0.05),上调TIMP-1、TIMP-2的活性(F=636.354,P<0.05,F=87.516,P<0.05)、mRNA(F=9.000,P<0.05,F=10.288,P<0.05)及蛋白表达水平(F=39.329,P<0.05,F=12.148,P<0.05),并使得MMP-2/TIMP-2、MMP-9/TIMP-1减小,P<0.05。结论白藜芦醇能有效抑制宫颈癌侵袭和转移。其作用机制可能与降低宫颈癌细胞运动能力、抑制MMP-2、MMP-9的活性、mRNA及蛋白表达水平,上调TIMP-1、TIMP-2的活性、mRNA及蛋白表达水平,并使得MMP-2/TIMP-2、MMP-9/TIMP-1减小,MMP-2/TIMP-2、MMP-9/TIMP-1的平衡能力相应提高有关。OBJECTIVE： To investigate the effects of resveratrol on the invasion and metastasis of cervical cancer in vitro. METHODS： The effects of resveratrol on invasive ability of HeLa cells were observed with a transwell cell culture chamber. The activities of MMP-2 and MMP-9 were analyzed using gelatin zymography.The activities of TIMP-1 and TIMP-2 were analyzed using reverse zymography.The mRNA expressions of MMP-2, MMP-9, TIMP-1 and TIMP-2 in HeLa cells were detected by RT-PCR. And the protein expressions of them were detected by Western blotting. RESULTS： The means of invading HeI.a cells in both the groups of 1, 0.5 mmol/L, resveratrol were 9.20±1. 924,10.20±2. 049. Compared with the control group （39.80±2.387）, those were significantly smaller,P〈0.05. The activities of MMP-2 and MMP-9 can be markedly inhibited by resveratrol, and the levels of mRNA and protein of MMP-2 and MMP-9 were also decreased by resveratrol （P〈0.05）. On the contrary, the proteinase activities and the mRNA and protein expressions of TIMP-1 and TIMP-2 could be increased by resveratrol （activities： F=636.354, P〈0.05, F=87.516, P〈0.05;mRNA： F= 9. 000, P〈0. 05, F= 10.288, P〈0.05;protein：F=39.329,P〈0.05,F=12.148,P〈 0.05）. Meanwhile the ratios of MMP-2/TIMP-2, MMP-9/TIMP-1 was reduced （P〈0.05）. CONCLUSIONS： Resveratrol can effectually inhibit the migration and invasion of HeLa cells in vitro. The mechanism may be related to down-regulate the expressions and the activities of MMP2 and MMP-9,increase the expressions and the activities of TIMP-1 and TIMP-2, reduce the ratios of MMP-2/TIMP-2, MMF-9/TIMP-1 and increase the balance ability between them.

关 键 词：宫颈肿瘤 白藜芦醇 基质金属蛋白酶-2 基质金属蛋白酶-9 基质金属蛋白酶组织抑制剂-1 基质金属蛋白酶组织抑制剂-2 肿瘤侵袭 肿瘤转移 

分 类 号：R737.33[医药卫生—肿瘤]