外胚层发育不良蛋白-A受体相关死亡域在前列腺癌中的表达及其对细胞增殖、侵袭的影响  

The expression of ectodermal dysplasia protein-A receptor related death domain in prostate cancer and its effects on cell proliferation,migration,and invasion

作　　者：方志伟 杨小明[1] 魏晓松 樊鑫 张刘辉[1] Fang Zhiwei;Yang Xiaoming;Wei Xiaosong;Fan Xin;Zhang Liuhui(Department of Urology,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450000,China)

机构地区：[1]郑州大学第一附属医院泌尿外科,郑州450000

出　　处：《中华实验外科杂志》2023年第12期2451-2454,共4页Chinese Journal of Experimental Surgery

摘　　要：目的检测外胚层发育不良蛋白-A受体相关死亡域(EDARADD)在前列腺癌组织及细胞中的表达水平,探讨EDARADD对前列腺癌细胞生物学功能的影响及其机制。方法收集郑州大学第一附属医院泌尿外科2013年1月1日至2019年1月1日前列腺癌根治术石蜡病理121例,配对癌旁组织石蜡病理50例,采用免疫组织化学检测前列腺癌患者及正常前列腺组织中EDARADD蛋白的表达水平,并分析EDARADD表达与患者预后的关系。在前列腺癌细胞系DU145中转染小干扰RNA(siRNA)-EDARADD,将细胞分为对照组(shctrl)及转染组(shEDARADD)采用蛋白质印迹法(Western blot)验证转染效率。采用荧光细胞增殖实验检测细胞增殖能力,采用Matrigel检测细胞侵袭能力。采用Western blot检测蛋白激酶B(Akt)、磷酸化Akt(p-Akt)、雷帕霉素靶蛋白(mTOR)、磷酸化mTOR(p-mTOR)表达水平,两组间比较采用t检验。结果免疫组织化学显示EDARADD在前列腺癌中表达水平显著高于正常前列腺组织,且表达水平与肿瘤恶性程度呈正相关(χ^(2)=6.770,P<0.05)。EDARADD与前列腺癌患者无生化复发生存期负相关[(59.992±5.079)个月比(44.517±6.125)个月,χ^(2)=8.251,P<0.05],shEDARADD转染成功后,对照组在3、5 d时细胞增殖数目高于转染组[DU145细胞系shctrl比shEDARADD1为,3 d:(396.00±36.71)个比(80.67±11.24)个;5 d:(1747.30±110.29)个比(185.33±3.51)个,t=14.221、24.522,P<0.05;shctrl比shEDARADD2为,3 d:(396.00±36.71)个比(91.33±6.50)个;5 d:(1747.30±110.29)个比(270.67±18.58)个,t=14.152、22.872,P<0.05]。Matrigel实验中对照组侵袭细胞数目高于转染组[DU145细胞系shctrl比shEDARADD1为(123.50±13.01)个比(15.71±5.47)个,t=20.322,P<0.01;shctrl比shEDARADD2为(123.50±13.01)个比(15.14±4.30)个,t=20.962,P<0.05];Western blot实验显示转染组p-Akt及p-mTOR表达水平显著降低。结论EDARADD在前列腺癌组织中异常高表达,可作为癌基因促进前列腺癌发生发展。Objective To investigate the expression level of ectodermal dysplasia protein-A receptor related death domain(EDARADD)in prostate cancer tissues and cells,and to explore the effect and mechanism of EDARADD on the biological function of prostate cancer cells.Methods From January 1,2013 to January 1,2019,121 cases of adenocarcinoma undergoing radical surgery and 50 cases of paired paracancerous tissue paraffin pathology were collected in our hospital.The expression level of EDARADD protein was detected by immunohistochemistry in prostate cancer patients and normal prostate tissue,and the relationship between EDARADD expression and patient prognosis was analyzed.Transfecting small interfering RNA(siRNA)-EDARADD into prostate cancer cell line DU145,the cells were divided into a control group(shctrl)and a transfection group(shEDARADD),and the transfection efficiency was verified using Western blotting.Fluorescent cell proliferation assay was used to detect cell proliferation ability,and Matrigel was used to detect cell invasion ability.Western blotting was used to detect the expression levels of protein kinase B(Akt),phosphorylated Akt(p-Akt),mammalian target of rapamycin(mTOR),and phosphorylated mTOR(p-mTOR),and t-test was used for comparison between the two groups.Results The results of immunohistochemistry showed that the expression level of EDARADD in prostate cancer was significantly higher than that in normal prostate tissue,and the expression level was positively correlated with the degree of malignancy of the tumor(χ^(2)=6.770,P<0.05).EDARADD is negatively correlated with non biochemical recurrence survival in prostate cancer patients[(59.992±5.079)months compared to(44.517±6.125)months,χ^(2)=8.251,P<0.05].After successful transfection of shEDARADD,the number of cell proliferation in the control group was higher than that in the transfected group at 3 d and 5 d,and the DU145 cell line shctrl was higher than shEDARADD(3 d:396.00±36.71 vs.80.67±11.24;5 d:1747.30±110.29 vs.185.33±3.51,t=14.221,24.522,P<0.

关 键 词：外胚层发育不良蛋白-A受体相关死亡域 前列腺癌 增殖 侵袭 

分 类 号：R737.25[医药卫生—肿瘤]