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

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.

Matriptase-Induced Phosphorylation of MET is Significantly Associated with Poor Prognosis in Invasive Bladder Cancer; an Immunohistochemical Analysis

“…It has been reported that HAI-1 is expressed in various epithelial cells, and possible suppressive role in cancer progression [8]. Reduced HAI-1 expression reported to be associated with poor prognosis in patients with prostatic, breast, ovarian and endometrial cancer [38,39,40,41,42]. Interestingly, in our investigation, patients with high expression of matriptase and low expression of HAI-1 had significantly poorer prognosis compared with patient with the opposite expression despite the absence of correlation between HAI-1 expression and cancer-specific survival.…”

PGC-1α and ERRα in patients with endometrial cancer: a translational study for predicting myometrial invasion

“…The scratch areas in the wells were washed with PBS and 1 mmol/L R-flurbiprofen until the cells in those areas were removed thoroughly and imaged at 0 and 24 h post-scratching. The horizontal migration rate was calculated using the following formula: (width 0 h − width 24 h )/width 0 h × 100% [ 34 ].…”

“…After incubation for 24 h, non-invading cells on the top of the filter were removed with a cotton swab, and the filters were fixed with methanol and stained with crystalline violet. The filters were removed from the inserts and mounted onto slides for imaging and quantification as described in a previous study [ 34 ].…”

Potential role of the HOXD8 transcription factor in cisplatin resistance and tumour metastasis in advanced epithelial ovarian cancer

“…Lentivirus mediated overexpressing HOXD8 vector or control vector were constructed and purchased from Genechem Company (GCD0161567, Shanghai, China). The OVCAR-3 and HO-8910 cells were infected with lentivirus mediated control vector (NC group) or overexpressing HOXD8 vector (OV group) at multiplicities of infection (MOIs) of 20 (low MOI) and 80 (high MOI) as our previous reported 48 . After infection for 72 h, GFP expression was detected to calculate the infection efficiency, and cells were harvested in fifth day after infection.…”