N-甲基亚硝基脲诱导膀胱癌大鼠模型中PI3K/AKT/mTOR信号通路与肿瘤组织凋亡的机制研究  

Research on PI3K/AKT/mTOR signal pathway and tumor tissue apoptosis in N-methyl-N-nitrosourea induced bladder cancer rat model

作　　者：刘宁[1] 谢斌[1] 敖晓晓[2] Liu Ning;Xie Bin;Ao Xiaoxiao(Department of Urology,Ba'nan People's Hospital of Chongqing City,Chongqing 401320,China;Department of Emergency,the Children's Hospital Affiliated to Chongqing Medical University,Chongqing 400015,China)

机构地区：[1]重庆市巴南区人民医院泌尿外科,重庆401320 [2]重庆医科大学附属儿童医院急诊科,重庆400015

出　　处：《国际泌尿系统杂志》2022年第3期444-447,共4页International Journal of Urology and Nephrology

基　　金：重庆市卫生计生委科技计划项目(2015XMSB000431)。

摘　　要：目的探索N-甲基亚硝基脲(MNU)诱导膀胱癌大鼠模型中PI3K/AKT/mTOR信号通路与肿瘤组织凋亡的机制。方法选取6~7周龄SD大鼠30只,随机分为对照组、造模组及抑制剂组,每组10只。造模组和抑制剂组使用MNU诱导膀胱癌大鼠模型,抑制剂组给予PI3K抑制剂,对照组和造模组给予等量的生理盐水。观察三组大鼠的膀胱形态学,对膀胱组织进行TUNEL染色,采用免疫印迹法(Western blot)检测组织中p-AKT、mTOR、Bcl-2、Bax蛋白的表达。结果抑制剂组的大体标本肿瘤体积和肿瘤数量均较造模组改善;TUNEL染色结果显示,抑制剂组的阳性细胞评分高于对照组和造模组,差异均有统计学意义(均P<0.05);Western blot法检测结果显示,抑制剂组的p-AKT、p-mTOR蛋白表达含量较其他两组显著下降,差异均有统计学意义(均P<0.01);抑制剂组的Bcl-2/Bax比率较其他两组显著下降,差异均有统计学意义(均P<0.01)。结论MNU诱导膀胱癌大鼠模型中肿瘤组织的凋亡可能与调节PI3K/AKT/mTOR信号通路有关。Objective To explore the mechanism of PI3K/AKT/mTOR signaling pathway and tumor tissue apoptosis in a rat model of bladder cancer induced by N-methyl-N-nitrosourea(MNU).Methods Thirty Sprague-Dawley(SD)rats aged 6-7 weeks were randomly divided into control group,model group,and inhibitor group.Model and inhibitor groups were given MNU to induce bladder cancer rat model,inhibitor group was given PI3K inhibitor,control group and model group were given the same amount of normal saline.The morphology of the rat bladders were observed,the bladder tissue was stained with TUNEL,and the protein expression of p-AKT,p-mTOR,Bcl-2,and Bax was detected by Western blot.Results The tumor volume and the number of tumors in the general specimens of the inhibitor group were improved compared with the model group.The scores of positive cells of the TUNEL staining in inhibitor group were higher than those of the control group and the model group.Western blot detection of p-AKT,p-mTOR,Bcl-2,Bax protein expression found that p-AKT,p-mTOR protein level and Bcl-2/Bax ratio in the inhibitor group were lower than the other two groups,the differences were statistical significance(all P<0.01).Conclusions MNU induced tumor tissue apoptosis in rat models of bladder cancer may be related to the regulation of PI3K/AKT/mTOR signaling pathway.

关 键 词：膀胱肿瘤 疾病模型 动物 大鼠 甲基亚硝脲 细胞凋亡 

分 类 号：R737.14[医药卫生—肿瘤] R-332[医药卫生—临床医学]