Interference Of HIF-1α By RNA To Reduce The Expression Of Matrix Metalloproteinase-2 In HeLa Cell Tumor Of Human Cervical Carcinoma

ObjectiveHypoxia inducible factor-1alpha (HIF-1α) is a hypoxic respondent regulatory factor, which is very common in the tissue of solid tumor. It plays crucial roles in maintaining cell energy metabolism, tumor angiogenesis, metastasis, cell proliferation and apoptosis. This study was to investigate the effect of silencing HIF-1αby RNA interference on expression of matrix metalloproteinase-2 (MMP-2) in HeLa cell tumor of human cervical carcinoma, and to approach its mechanism initially.Methods1 15 nude mice were divided into three groups randomly, the blank control group, the negative control group and the experimental group. The above three groups were inoculated with HeLa cells, pGenesil-1-HeLa cells, HIF-1α-HeLa cells respectively;2 The expression of HIF-1α, E-cadherin,β-catenin, MMP-2 in xenograft tumors of nude mice were detected by immunohistochemistry;3 HeLa cells which transfected with pGenesil-1 plasmid (pGenesil-1-HeLa cells), or plasmid conducted with short hairpin RNA (HIF-1α-HeLa cells) were cultured under hypoxia and normoxia for 48 h respectively, untransfected HeLa cells were cultured under the same condition as control. Western blot were used to detect the expression of HIF-1α, E-cadherin,β-catenin and MMP-2 in the cells of each group.Results1 The immunohistochemistry stain showed the expression of HIF-1α, E-cadherin,β-catenin, MMP-2 in the xenograft tumor of nude mice respectively, in blank control group were (69.0±12.1) %, (17.0±3.6) %, (56.0±7.9) %, (60.0±5.0) %; in negative control group were (62.8±12.3) %, (19.0±5.9) %, (53.0±6.9) %, (58.0±7.4) %, in exper- imental group were (17.4±8.8) %, (51.0±9.9) %, (24.0±2.6) %, (23.0±4.6) %;2 HIF-1αand MMP-2 have positive correlation with each other, the coefficient correlation was 0.521 (P =0.035) by statistical analysis;3 The western blot showed a high expression of HIF-1α,β-catenin, MMP-2 protein in HeLa cells, pGenesil-1-HeLa cells under hypoxia for 48 h, and E-cadherin protein in HIF-1α-HeLa cells under hypoxia or normoxia for 48 h, and a weakly expression ofβ-catenin, MMP-2 protein in HIF-1α-HeLa cells and E-cadherin protein in HeLa cells, pGenesil-1-HeLa cells under hypoxia or normoxia for 48 h, and a weakly expression of HIF-1αin HeLa cells, pGenesil-1-HeLa cells, HIF-1α-HeLa cells under normoxia for 48 h and in HIF-1α-HeLa cells under hypoxia for 48 h.ConclusionIn the HeLa cells of human cervical carcinoma Hela cells, inhibiting the HIF-1αcould effectively down-regulate the expression of MMP-2. They have positive correlation with each other. And the possible mechanism might has some relationships with the compound of the E-cd/cat.