胰高血糖素样肽1受体在子宫内膜癌中的表达及意义研究  

Expression and significance of glucagon-like peptide 1 receptor in endometrial carcinoma

作　　者：李武[1] 刘松君[1] 阮凡[1] 吕雯 LI Wu;LIU Songjun;RUAN Fan;LYU Wen(Department of Gynecology,Tongde Hospital of Zhejiang Province,Hangzhou 310012,China)

机构地区：[1]浙江省立同德医院妇科,杭州310012

出　　处：《浙江医学》2022年第19期2039-2043,2048,I0004,共7页Zhejiang Medical Journal

基　　金：浙江省医药卫生科技计划项目(2018ZD016);浙江省基础公益研究计划项目(LGF20H160013)。

摘　　要：目的分析胰高血糖素样肽1受体(GLP1R)在子宫内膜癌(EC)组织、细胞中的表达情况,并探讨GLP1R对EC细胞活力的影响。方法选取2019年至2020年在浙江省立同德医院行手术治疗的EC患者5例,收集EC患者内膜组织和配对的正常内膜组织。购买的5种人EC细胞系分别为HEC-1A、RL95-2、KLE、Ishikawa和AN3CA。分别采用RT-qPCR法、Western blot法检测EC组织或细胞GLP1R mRNA、蛋白表达水平;采用免疫组化法定性检测EC组织GLP1R蛋白表达情况;采用靶向GLP1R的小干扰RNA(siRNA)转染AN3CA细胞,或用GLP-1类似物exendin-4处理AN3CA细胞,采用CCK-8法检测转染后细胞活力。结果EC组织GLP1R mRNA、蛋白表达水平均高于正常内膜组织(均P<0.05)。免疫组化检测显示,GLP1R蛋白主要在肿瘤细胞膜上表达。5种EC细胞(HEC-1A、RL95-2、KLE、Ishikawa和AN3CA)中,AN3CA细胞GLP1R mRNA、蛋白表达水平高于其他4种细胞(均P<0.05)。转染siRNA的AN3CA细胞GLP1R mRNA表达水平均低于未转染的AN3CA细胞(对照组)(均P<0.05);AN3CA细胞用GLP-1类似物exendin-4处理后,GLP1R mRNA表达水平明显高于对照组细胞(P<0.05)。在培养48、72 h时,exendin-4处理的AN3CA细胞存活率高于对照组(P<0.05),转染siRNA后的AN3CA细胞存活率低于转染siNC(阴性对照)的AN3CA细胞(P<0.05)。结论EC组织和细胞中GLP1R表达上调,其表达上调促进EC细胞增殖,加速EC的进展。GLP1R可能在EC细胞中发挥致癌基因功能。GLP1R或可成为EC的生物标志物和治疗EC的生物靶点。Objective To investigate the expression of glucagon-like peptide 1 receptor(GLP1R)in endometrial carcinoma(EC)tissues and cells,and to explore the effect of GLP1R on EC cell viability.Methods The endometrial cancer tissues and matched normal endometrial tissues were collected from 5 EC patients who underwent surgical treatment in Tongde Hospital of Zhejiang Province from 2019 to 2020.RT-qPCR and Western blot were used to detect the expression levels of GLP1R mRNA and protein in EC tissues or EC cell lines;immunohistochemistry was used to qualitatively detect the expression of GLP1R protein in EC tissues.Small interfering RNA(siRNA)targeting GLP1R or GLP-1 analog exendin-4 were transfect to EC AN3CA cells,and the cell viability after transfection was detected by CCK 8 method.Results The expression levels of GLP1R mRNA and protein in EC tissues were higher than those in normal endometrial tissues(all P<0.05).Immunohistochemical detection showed that GLP1R protein was mainly expressed on the tumor cell membrane.Among EC cell lines HEC 1A,RL95-2,KLE,Ishikawa and AN3CA,the expression levels of GLP1R mRNA and protein in AN3CA cells were the highest(all P<0.05).The expression level of GLP1R mRNA in AN3CA cells transfected with siRNA was lower than that in untransfected AN3CA cells(control group)(P<0.05).After AN3CA cells were treated with GLP-1 analog exendin-4,the expression level of GLP1R mRNA was significantly higher compared with the control cells(P<0.05).At 48 and 72 h of culture,the viability of exendin-4-treated AN3CA cells was higher than that of the control group(P<0.05),and the viability of AN3CA cells transfected with siRNA was lower than that of AN3CA cells transfected with siNC(negative control)(P<0.05).Conclusion The expression of GLP1R is up-regulated in EC tissues and cell lines,and its up-regulation promotes the proliferation of EC cells and accelerates the progression of EC,indicating that GLP1R may be used as a biomarker of EC and a biological target for the treatment of EC.

关 键 词：子宫内膜癌 胰高血糖素样肽1受体 细胞增殖 细胞周期 

分 类 号：R737.33[医药卫生—肿瘤]