Decreasing the ratio of matriptase/HAI-1 by down-regulation of matriptase show a potential adjuvant therapy in ovarian cancer
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.
Matriptase HAI-1 Ovarian cancer RNA interference Invasion Metastasis
Pengming Sun Zhongqing Jiang Xiaofang Chen Lifang Xue Xiaodan Mao Guanyu Ruan Yiyi Song Alexander Mustea
Institute of Gynecologic Oncology,Fujian Maternity and Children Health Hospital,Teaching Hospital of Department of Gynecology,Xiamen Hospital of Traditional Chinese Medicine,No.1739,Xian Yue Load,Xiame Gynecological Tumor Center,Department of Obstetrics and Gynecology,Medical University Greifswald,Fer
国内会议
广州
英文
515-523
2015-09-10（万方平台首次上网日期，不代表论文的发表时间）