脑恶性肿瘤缺失基因1对子宫内膜癌的作用及其机制

The effectand mechanism of deleted in malignant brain tumors1 on endometrial cancer

目的:探究脑恶性肿瘤缺失基因1(DMBT1)对子宫内膜癌的作用及其可能的作用机制。方法:收集子宫内膜癌组织(子宫内膜癌组)及正常对照组织(正常对照组)各31例,RT-PCR和免疫组化(IHC)检测组织中DMBT1 mRNA和蛋白表达;选取人子宫内膜上皮细胞EEC(EEC组)和人子宫内膜癌细胞Ishikawa(Ishikawa组)进行体外研究,将Ishikawa细胞随机分为空白对照组、阴性对照(NC)组、DMBT1组和DMBT1+galectin-3组,按照分组进行DMBT1和galectin-3过表达载体及其NC的转染,RT-PCR检测细胞中DMBT1 mRNA表达;Western blotting检测细胞中DMBT1和galectin-3蛋白表达;CCK-8检测细胞增殖;Transwell实验检测细胞迁移和侵袭。结果:子宫内膜癌组中DMBT1 mRNA表达和IHC评分较正常对照组明显降低(P<0.05)。子宫内膜癌细胞中DMBT1 mRNA和蛋白表达较子宫正常细胞明显降低(P<0.05)。DMBT1组细胞中DMBT1蛋白表达较NC组明显升高(P<0.05),细胞在24 h、48 h和72 h的OD值较NC组明显降低(P<0.05),细胞迁移数和侵袭数较NC组明显降低(P<0.05),galectin-3蛋白表达较NC组明显降低(P<0.05);DMBT1+galectin-3组细胞中galectin-3蛋白表达较DMBT1组明显升高(P<0.05),细胞在48 h和72 h的OD值较DMBT1组明显升高(P<0.05),细胞迁移数和侵袭数较DMBT1组明显升高(P<0.05)。结论:子宫内膜癌组织中DMBT1表达下调,DMBT1可能通过抑制galectin-3的表达,从而抑制子宫内膜癌细胞增殖、迁移和侵袭。

Objective:To explore the effect of deleted in malignant brain tumors 1(DMBT1)on endometrial cancer and its possible mechanism.Methods:A total of 31 cases of endometrial cancer tissues and 31 normal control tissues were collected.RT-PCR and immunohistochemistry(IHC)were respectively used to detect the expression of DMBT1 mRNA and protein in the tissues.Human endometrial epithelial cells EEC and human endometrial cancer cells Ishikawa were selected for in vitro study.Ishikawa cells were randomly divided into blank control group,negative control(NC)group,DMBT1 group and DMBT1+galectin-3 group.The DMBT1,galectin-3 overexpression vector and its NCwere transfected into cellsby grouping.RT-PCR was used to detect the DMBT1 mRNA expression.Western blotting was used to determined the protein expression of DMBT1 and galectin-3.CCK-8 method was used to detect cell proliferation.Transwell experiment was performed to detect cell migration and invasion.Results:The DMBT1 mRNA expression and IHC score in endometrial carcinoma tissueswere significantly lower than those in normal controls(P<0.05).The expression of DMBT1 mRNA and protein in Ishikawa cells was significantly lower than that in EEC cells(P<0.05).The DMBT1 protein expression in the DMBT1 group was significantly higher than that in the NC group,whereas the OD valueat 24 h,48 h and 72 h,the number of migration and invasion cells,and the expression of galectin-3 protein were significantly lower(P<0.05).The expression of galectin-3 protein in the DMBT1+galectin-3 group was significantly higher than that in the DMBT1 group,whilethe OD value at 48 h and 72 h andthe number of migration and invasion cells were-significantly higher(P<0.05).Conclusion:The expression of DMBT1 was down-regulated in endometrial cancer tissues.DMBT1 may inhibit the proliferation,migration and invasion of endometrial cancer cells by suppressing the expression of galectin-3.