NRAGE对结直肠癌细胞增殖和侵袭能力的作用机制  

The mechanism of NRAGE on the proliferation and invasion of colorectal cancer cells

作　　者：周堤侠 吕海栋[1] 金秉巾[2] 刘国庆[1] Zhou Dixia;LüHaidong;Jin Bingjin;Liu Guoqing(Dept of Oncology,Qinghai Provincial People′s Hospital,Xining 810001;Dept of Pharmacy,Qinghai Provincial People′s Hospital,Xining 810001)

机构地区：[1]青海省人民医院肿瘤外科,西宁810001 [2]青海省人民医院药学科,西宁810001

出　　处：《安徽医科大学学报》2022年第1期84-89,共6页Acta Universitatis Medicinalis Anhui

基　　金：青海省卫生计生委科研课题(编号:2018-ZJ-075)。

摘　　要：目的研究神经营养蛋白受体相互作用的同源物(NRAGE)对结直肠癌(CRC)细胞增殖和侵袭能力的作用机制。方法选取84例CRC患者的临床病理材料,应用荧光定量PCR(qPCR)及免疫印迹实验检测CRC组织及癌旁正常组织中NRAGE的表达,分析癌组织中NRAGE的表达与临床病理特征的关系。RT-PCR及免疫印迹实验检测CRC肿瘤细胞系HT29、SW480、SW620、LOVO及结直肠正常细胞系FHC中NRAGE mRNA及蛋白表达。MTT实验、Transwell迁移实验观察NC组、过表达NRAGE组及NRAGE敲低组肿瘤细胞增殖及迁移能力。qPCR及免疫印迹实验检测各组AKT、p-AKT、ERK1/2、p-ERK1/2、E-cadherin、N-cadherin、Vimentin的表达差异。结果与癌旁组织相比,CRC癌组织中NRAGE的mRNA及蛋白表达明显升高。癌组织中NRAGE的表达与肿瘤分期、远处转移及淋巴结转移有关(P<0.05)。与FHC细胞相比,CRC肿瘤细胞系HT29、SW480、SW620、LOVO细胞中NRAGE的mRNA及蛋白表达较高(P<0.05)。与NC相比,过表达NRAGE组的CRC肿瘤细胞增殖及迁移能力明显增强,而敲低组增殖及迁移能力明显减弱。与NC组相比,过表达NRAGE组SW480细胞p-ERK1/2蛋白表达较高,而ERK1/2、AKT及p-AKT表达无明显差异。予过表达NRAGE组SW480细胞应用ERK抑制剂U0126后,SW480细胞的增殖及迁移能力明显降低。结论NRAGE可通过激活ERK信号通路,促进CRC细胞上皮间质转化,增强CRC肿瘤细胞的增殖及迁移能力。Objective To study the mechanism of neurotrophin receptor-interacting MAGE homolog(NRAGE)on the proliferation and invasion of colorectal cancer(CRC)cells.Methods The clinicopathological data of 84 CRC patients were selected.Fluorescence quantitative PCR(qPCR)and Western blot were used to detect the expression of NRAGE in CRC tissues and adjacent normal tissues.The relationship between the expression of NRAGE in cancer tissues and clinicopathological characteristics was analyzed statistically.RT-PCR and Western blot were used to detect the expression of NRAGE mRNA and protein in CRC tumor cell lines HT29,SW480,SW620,LOVO and colorectal normal cell line FHC.MTT proliferation experiment and Transwell migration experiment were used to observe the tumor cell proliferation and migration ability of the NC group,overexpression NRAGE group and NRAGE knockdown group.The expression differences of AKT,p-AKT,ERK1/2,p-ERK1/2,E-cadherin,N-cadherin and Vimentin were detected by qPCR and Western blot.Results Compared with adjacent tissues,NRAGE mRNA and protein expression in CRC cancer tissues were significantly higher.The expression of NRAGE in cancer tissues was related to tumor stage,distant metastasis and lymph node metastasis(all P<0.05).Compared with FHC cells,CRC tumor cell lines HT29,SW480,SW620,and LOVO cells had higher NRAGE mRNA and protein expression(P<0.05).Compared with the NC group,the proliferation and migration ability of CRC tumor cells in the overexpression NRAGE group was significantly enhanced,while the knockdown group was significantly weakened.Compared with the NC group,the SW480 cells in the overexpression NRAGE group had higher p-ERK1/2 protein expression,but there was no significant difference in the expression of ERK1/2,AKT and p-AKT.After the SW480 cells in the overexpression NRAGE group were treated with ERK inhibitor U0126,the proliferation and migration ability of SW480 cells significantly reduced.Conclusion NRAGE can promote the epithelial-mesenchymal transition of CRC cells and enhance the prolife

关 键 词：结直肠癌 NRAGE 上皮间质转化 增殖 迁移 

分 类 号：R735.34[医药卫生—肿瘤]