膀胱癌组织黑色素瘤抗原-A3的表达及其对核因子KappaB信号通路的影响  

Expression of MAGE-A3 in bladder carcinoma and regulatory role in NF-κB Signaling pathway-related inflammatory factors

作　　者：周高峰[1] 黄智红[2] 吕磊[1] 向威[1] 孙莹[1] 朱金燕[1] 袁敬东[1] 章传华[1] 吴维[1] Gao-feng Zhou;Zhi-hong Huang;lei Lu;Wei Xiang;Ying Sui;Jin-yan Zhu;Jing-dong Yuan;Chuan-hua Zhang;Wei Wu(Department of Urology,the First Hospital of Wuhan City,Wuhan,Hubei 430022,China;Department of Hematology,the First Hospital of Wuhan City,Wuhan,Hubei 430022,China)

机构地区：[1]湖北省武汉市第一医院泌尿外科,湖北武汉430022 [2]湖北省武汉市第一医院血液内科,湖北武汉430022

出　　处：《中国现代医学杂志》2018年第21期36-41,共6页China Journal of Modern Medicine

基　　金：湖北省武汉市卫生和计划生育委员会科研项目(No:WX16B04)

摘　　要：目的探讨膀胱癌组织中黑色素瘤抗原-A3(MAGE-A3)的表达变化及其对核因子Kappa B(NF-κB)信号通路相关炎症因子表达的影响。方法依照纳入与排除标准,收集该院膀胱癌患者120例。实时荧光定量PCR(q RT-PCR)和Western blot检测膀胱癌组织中MAGE-A3 m RNA和蛋白的表达变化;ELISA检测膀胱癌组织中NF-κB信号通路相关炎症因子如肿瘤坏死因子α(TNF-α)和白介素1β(IL-1β)的表达变化;分析MAGE-A3阳性率和炎症因子含量与年龄、性别、肿瘤组织类型及肿瘤分期等的关系;培养膀胱癌细胞系T24,采用小干扰RNA(si RNA)敲减MAGE-A3的表达后,检测NF-κB P65磷酸化水平变化及TNF-α和IL-1β的表达变化。结果膀胱癌组织中MAGE-A3 m RNA、蛋白及炎症因子的表达水平高于正常膀胱组织,差异有统计学意义(P<0.01);MAGE-A3阳性率及患者肿瘤组织中炎症因子含量与一般临床资料无相关,而与膀胱癌分期呈正相关;si RNA敲减MAGE-A3的表达后,NF-κB p65磷酸化水平及TNF-α和IL-1β的表达水平均降低,差异有统计学意义(均P<0.01)。结论 MAGE-A3可能通过NF-κB信号通路调控膀胱癌细胞炎症状态,促进膀胱癌的发生发展。Objective To investigate the expression of melanoma-associated antigen-A3(MAGE-A3)in bladder carcinoma and its regulatory effect on the expression of Nuclear Factor kappa B(NF-κB)signaling pathway related inflammatory factors.Methods Totally 120 cases of bladder cancer were involved in this study based on inclusion and exclusion criteria.RT-qPCR and Western blot were used to detect the expression of MAGE-A3 in bladder cancer tissues.ELISA assay was performed to detect the expression of NF-κB signaling related factors such as tumor necrosis factor alpha(TNF-α)and interleukin 1β(IL-1β).Association between MAGE-A3 positive rate or inflammatory factor content and age,sex,tumor type and tumor staging were determined.MAGE-A3 was knocked down by small interfering RNA(siRNA)in bladder cancer cell line T24.Results Expression of MAGE-A3 and inflammatory factor in bladder cancer tissues was significantly higher than that in normal bladder tissues(P<0.01).The positive rate of MAGE-A3 and the content of inflammatory factors in tumor tissue were not correlated with general clinical data while positively associated with the stage of bladder cancer.SiRNA knockdown of MAGE-A3 induced significant reduction of NF-κB p65 phosphorylation levels and TNF-αand IL-1βexpression levels((P<0.01).Conclusion MAGE-A3 regulates the inflammatory response and promote the development of bladder cancerthrough NF-κB signaling pathway.

关 键 词：膀胱癌 MAGE-A3 NF-ΚB信号通路 p65磷酸化 炎症因子 

分 类 号：R737.14[医药卫生—肿瘤]