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.
Highlights
Endometrial cancer is one of the most common malignancies of the female reproductive tract, and its incidence is currently increasing
Messenger ribonucleic acid 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 Messenger ribonucleic acid (mRNA) expression of matriptase and HAI-1 was detected by The levels of matriptase and HAI-1 mRNA expression in HEC-1A, HEC-1B, and RL-952 endometrial cancer cell lines were determined using quantitative PCR
Summary
Endometrial cancer is one of the most common malignancies of the female reproductive tract, and its incidence is currently increasing. The American Cancer Society estimated there would be 60,050 new cases and 10,470 deaths from endometrial cancer in 2016 [1] Asian nations such as China, Japan, and Korean have lower incidence than do western industrialized countries. The incidence of endometrial cancer in China has increased over the past 30 years, and it is currently the second most common gynecologic malignancy [2]. Optimal treatment approaches yield response rates of 40–70% in patients www.impactjournals.com/oncotarget with primary advanced cancer and 15–30% in patients with recurrent disease. Among these patients, median progression-free survival is only 6 months and median overall survival is 12 months [5]. Studies on the invasive and metastatic mechanism are essential to improve advanced endometrial cancer-related survival and cure rate
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