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

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 HeLa 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,P0.05. 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 (P0.05). 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, P0.05, F=87.516, P0.05;mRNA: F=9.000,P0.05, F=10.288, P0.05;protein:F=39.329,P0.05,F=12.148,P0.05).Meanwhile the ratios of MMP-2/TIMP-2、MMP-9/TIMP-1 was reduced (P0.05). 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 MMP-2 and MMP-9,increase the expressions and the activities of TIMP-1 and TIMP-2, reduce the ratios of MMP-2/TIMP-2,MMP-9/TIMP-1 and increase the balance ability between them.