Regulation of matriptase and HAI-1 system, a novel therapeutic target in human endometrial cancer cells

// Pengming Sun 1, 2 , Lifang Xue 2 , Yiyi Song 2 , Xiaodan Mao 1 , Lili Chen 2 , Binhua Dong 1 , Elena Loana Braicu 3 and Jalid Sehouli 3 1 Laboratory of Gynecologic Oncology, Fujian Provincial Maternity and Children Hospital, Affiliate Hospital of Fujian Medical University, 350001 Fuzhou, Fujian, P.R. of China 2 Department of Gynecology, Fujian Provincial Maternity and Children Hospital, Affiliate Hospital of Fujian Medical University, 350001 Fuzhou, Fujian, P.R. of China 3 Department of Gynecologic Oncology and Gynecology, Charite, Campus Virchow-Klinikum, European Competence Center for Ovarian Cancer University of Berlin, 13353 Berlin, Germany Correspondence to: Pengming Sun, email: sunfemy@hotmail.com Keywords: matriptase; HAI-1; endometrial cancer; target therapy; cisplatin Received: March 01, 2017      Accepted: November 01, 2017      Published: January 03, 2018 ABSTRACT 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.