Sun Pengming, Xue Lifang, Song Yiyi, Mao Xiaodan, Chen Lili, Dong Binhua, Braicu Elena Loana, Sehouli Jalid
Laboratory of Gynecologic Oncology, Fujian Provincial Maternity and Children Hospital, Affiliate Hospital of Fujian Medical University, 350001 Fuzhou, Fujian, P.R. of China.
Department of Gynecology, Fujian Provincial Maternity and Children Hospital, Affiliate Hospital of Fujian Medical University, 350001 Fuzhou, Fujian, P.R. of China.
Oncotarget. 2018 Jan 3;9(16):12682-12694. doi: 10.18632/oncotarget.23913. eCollection 2018 Feb 27.
The effects of specific and non-specific regulation of matriptase on endometrial cancer cells 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 ( < 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 ( < 0.001). Moreover, the invasiveness, metastasis, and survival rate of HEC-1A and RL-952 endometrial cancer cells were significantly decreased ( < 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 ( = 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.
研究了基质金属蛋白酶（matriptase）特异性和非特异性调节对子宫内膜癌细胞的影响。通过实时定量聚合酶链反应（RT-qPCR）和蛋白质免疫印迹法检测了RL-952、HEC-1A和HEC-1B子宫内膜癌细胞中matriptase和肝细胞生长因子激活剂抑制剂-1（HAI-1）的信使核糖核酸（mRNA）和蛋白表达。用慢病毒介导的靶向matriptase的小干扰RNA（siRNA）（MA-siRNA）感染细胞或用不同浓度的顺铂（DDP）处理细胞。处理后，分析细胞的侵袭、迁移和凋亡情况。感染MA-siRNA后，matriptase的mRNA和蛋白表达显著下降至80%（P<0.01），划痕实验和Transwell小室实验显示侵袭性和转移性受到显著抑制。用高于治疗剂量的顺铂孵育24小时后，matriptase和HAI-1的表达显著下降（P<0.001）。此外，随着顺铂浓度增加，matriptase和HAI-1表达下调，导致HEC-1A和RL-952子宫内膜癌细胞的侵袭性、转移性和存活率显著下降（P<0.001）。然而，用低浓度顺铂处理的细胞中matriptase和HAI-1表达略有增加（P=0.01）。此外，matriptase表达与转移和侵袭有关。在matriptase/HAI-1阳性的子宫内膜癌细胞中，通过特异性Ma-SiRNA或非特异性顺铂下调matriptase显示出有前景的治疗特性。
