Regulation of matriptase and HAI-1 system, a novel therapeutic target in human endometrial cancer cells
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Pengming Sun1,2, Lifang Xue2, Yiyi Song2, Xiaodan Mao1, Lili Chen2, Binhua Dong1, Elena Loana Braicu3 and Jalid Sehouli3
1Laboratory of Gynecologic Oncology, Fujian Provincial Maternity and Children Hospital, Affiliate Hospital of Fujian Medical University, 350001 Fuzhou, Fujian, P.R. of China
2Department of Gynecology, Fujian Provincial Maternity and Children Hospital, Affiliate Hospital of Fujian Medical University, 350001 Fuzhou, Fujian, P.R. of China
3Department of Gynecologic Oncology and Gynecology, Charité, Campus Virchow-Klinikum, European Competence Center for Ovarian Cancer University of Berlin, 13353 Berlin, Germany
Pengming Sun, email: firstname.lastname@example.org
Keywords: matriptase; HAI-1; endometrial cancer; target therapy; cisplatin
Received: March 01, 2017 Accepted: November 01, 2017 Published: January 03, 2018
The effects of specific and non-specific regulation of matriptase on endometrial cancer cells in vitro were investigated. Messenger ribonucleic acid (mRNA) and protein expression of matriptase and hepatocyte growth factor activator inhibitor-1 (HAI-1) in RL-952, HEC-1A, and HEC-1B endometrial cancer cells were detected by real-time quantitative PCR (RT-qPCR) and western blot. The cells were infected with lentivirus-mediated small-interfering RNA (siRNA) targeted on matriptase (MA-siRNA) or treated with different cisplatin (DDP) concentrations. After treatment, invasion, migration, and cellular apoptosis were analyzed. Matriptase mRNA and protein expression significantly decreased to 80% after infection with MA-siRNA (P < 0.01), and scratch and trans-well chamber assays showed significant inhibition of invasiveness and metastasis. Upon incubation with cisplatin at concentrations higher than the therapeutic dose for 24 h, the expressions of matriptase and HAI-1 significantly decreased (P < 0.001). Moreover, the invasiveness, metastasis, and survival rate of HEC-1A and RL-952 endometrial cancer cells were significantly decreased (P < 0.001) due to the down-regulation of matriptase and HAI-1 upon increasing cisplatin concentration. However, a slight increase in matriptase and HAI-1 expression was observed in cells treated with low cisplatin concentration (P = 0.01). Moreover, matriptase expression was associated with metastasis and invasiveness. Down-regulation of matriptase by specific Ma-SiRNA or non-specific cisplatin in matriptase/HAI-1–positive endometrial cancer cells showed promising therapeutic features.
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