Tiam1基因沉默对胰腺癌细胞裸鼠移植瘤生长的影响  

Effect of silencing Tiam1 on growth of xenografts with pancreatic cancer in nude mice

作　　者：丁米娜 邓春玲 李月 朴英实 陈丽艳[1,2] DING Mi-Na;DENG Chun-Ling;LI Yue(Yanbian University Medical College,Yanji 133002,Jilin,China)

机构地区：[1]延边大学医学院生物化学与分子生物学,吉林延吉133002 [2]延边大学肿瘤研究中心

出　　处：《中国老年学杂志》2020年第4期843-846,共4页Chinese Journal of Gerontology

基　　金：国家自然科学基金(No.81660436)

摘　　要：目的研究沉默T淋巴瘤侵袭转移诱导因子(Tiam)1基因对胰腺癌细胞裸鼠移植瘤生长的影响,并探讨其可能的分子机制。方法通过RNA干扰(RNAi)技术沉默胰腺癌BxPC-3细胞中Tiam1的表达,Western印迹实验检测其沉默效果;将转染处理过的胰腺癌细胞接种于裸鼠皮下,建立胰腺癌皮下移植瘤模型;观察肿瘤生长情况并绘制肿瘤生长曲线,裸鼠处死后,取瘤称重;苏木素-伊红(HE)染色法观察移植瘤组织病理学结构;免疫组织化学染色法(IHC)检测移植瘤组织增殖相关蛋白Ki-67,转移相关蛋白E-钙黏蛋白(cadherin)、波形蛋白(Vimentin)、Slug的表达。结果RNAi技术可有效沉默胰腺癌BxPC细胞中Tiam1的表达,并成功构建胰腺癌裸鼠移植瘤模型;与对照组比较,si-Tiam1组裸鼠肿瘤体积与质量均明显降低(P<0.05);HE染色结果显示,与对照组比较,si-Tiam1组中肿瘤组织出现细胞皱缩、片状坏死等病理性改变;IHC结果显示,与对照组相比,si-Tiam1组移植瘤组织中Ki-67、Vimentin、Slug的表达明显降低,而E-cadherin的表达明显升高。结论沉默Tiam1能有效抑制胰腺癌裸鼠移植瘤的生长,其机制可能与Ki-67、Vimentin、Slug表达的降低及E-cadherin的表达增强有关,提示Tiam1有可能成为胰腺癌基因治疗的新靶标。Objective To investigate the effect of silencing Tiam1 on growth of xenografts with pancreatic cancer in nude mice and explore its molecular mechanism.Methods RNA interference(RNAi)was used to silence Tiam1 in pancreatic cancer BxPC-3 cell.Western blot was used to detect the silencing effect.The transfected BxPC-3 cells were inoculated subcutaneously into nude mice to establish a transplantation tumor model of pancreatic cancer.The tumor growth was observed and the growth curve was drawn.The tumors were separated and weighed after mice were sacrificed.The pathological changes were detected with hematoxylin&eosin(HE)staining.The expression of Ki-67,E-cadherin,Vimentin and Slug of BxPC-3 transplanted tumors were detected by immunohistochemical(IHC).Results Compared with the control group,the tumor volume and weight of the si-Tiam1 group were decreased.The HE staining results showed that,necrosis presentation,tumor cell shrinkage and other pathological morphological changes could be found in si-Taim1 group compared with control group.The expression of Ki-67,Vimentin and Slug were decreased,and the expression of E-cadherin was increased in the tumor tissues of the si-Tiam1 group compared with the control group by IHC.Conclusions The down-regulation of Tiam1 could effectively inhibit the growth of pancreatic cancer xenografts in nude mice,which might be related to up-regulating E-cadherin and down-regulating Ki-67,Vimentin,Slug,which suggests that Tiam1 may be an effective target for pancreatic cancer therapy.

关 键 词：TIAM1 胰腺癌 移植瘤 上皮间质转化 抑制 

分 类 号：R735.9[医药卫生—肿瘤]