Decreasing the ratio of matriptase/HAI-1 by down-regulation of matriptase show a potential adjuvant

来源 :2015中国医师协会妇产科医师大会 | 被引量 : 0次 | 上传用户:boyanfang
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  Tumor invasion and metastasis are complex biological processes.The matriptase and its endogenous inhibitor,hepatocyte growth factor activator inhibitor-1 (HAI-1) play important role in the invasion and metastasis.To evaluate the ratio of matriptase/HAI-1 and their potential therapeutic value in ovarian cancer,HO-8910 human ovarian cancer cells and its hmologous high-metastatic HO-8910PM cells were used as in vitro cellular models.The invasive and metastatic abilities and the expression of matriptase and HAI-1 in these cells were detected using scratch assays,transwell chamber assays,quantitative RT-PCR,western blotting and fluorescent immunocytochemistry.After infected with Lentivirus-mediated matriptase-targeting siRNA,cell cycle progression and apoptosis were also analyzed.The migration distance and number of trans-well cells were significantly higher for HO-8910PM cells than for HO-8910 cells.HO-8910PM cells had significantly higher ratio of matriptase/HAI-1 mRNA than HO-8910 cells (0.51 vs 0.24,about 2.2 fold).Compared to HO-8910 cells,the matriptase mRNA was increased about 3.6 fold in HO-8910PM cells while the HAI-1 mRNA was increased about 1.7 fold respectively Similarly increasing was also observed in protein expression (0.47 vs 0.24,1.9 fold).Migration and invasiveness were positively correlated with matriptase (r=0.994,P<0.01) and ratio of matriptase/HAI-1 (r=0.929,P<0.01).Down-regulation of matriptase resulted in inhibition of the invasive and metastatic abilities of HO-8910PM cells and cell cycle arresting in the G0/G1 phase (54.81% ± 0.34% vs.43.08% ± 0.47%) and increasing apoptosis (15.10% ± 0.81% vs.5.2% ± 0.39%).Ovarian cancer cellular metastasis and invasion was more depended on the activation of matriptase but not inhibition of HAI-1.Matriptase is a potential adjuvant therapeutic target for inhibiting ovarian cancer invasion and metastasis.
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