沉默IGFBP-1对人胃肠道间质瘤GIST882细胞生长的影响及其作用机制  

Effect of silencing IGFBP-1 on the growth of human gastrointestinal stromal tumor cells GIST882 and its mechanism

作　　者：朱贤章[1] 田伟力 田培力 李涛[1] ZHU Xianzhang;TIAN Weili;TIAN Peili;LI Tao(Department of Gastrointestinal Surgery,People´s Hospital of Xinjiang Uygur Autonomous Region,Urumqi 830001,China;Nursing Home,Affiliated Tumor Hospital of Xinjiang Medical University;Department of Breast Head and Neck Surgery,Affiliated Tumor Hospital of Xinjiang Medical University,Urumqi 830011,China)

机构地区：[1]新疆维吾尔自治区人民医院胃肠外科,乌鲁木齐830001 [2]新疆医科大学附属肿瘤医院宁养院,乌鲁木齐830011 [3]新疆医科大学附属肿瘤医院乳腺头颈外科

出　　处：《中国癌症防治杂志》2021年第2期164-169,共6页CHINESE JOURNAL OF ONCOLOGY PREVENTION AND TREATMENT

基　　金：新疆维吾尔自治区自然科学基金项目(2018D01C195)。

摘　　要：目的探讨胰岛素样生长因子结合蛋白1(IGFBP-1)在人胃肠道间质瘤中的表达及其对胃肠道间质瘤细胞生长的影响和作用机制。方法采用免疫组化染色检测IGFBP-1表达;人胃肠道间质瘤细胞GIST882分别转染siRNA-NC(siRNA-NC组)、siRNA-IGFBP-1(siRNA-IGFBP-1组),并设置空白对照组。采用qRT-PCR和Western blot实验检测IGFBP-1 mRNA和蛋白表达水平;CCK-8实验检测细胞活性;EDU实验检测细胞增殖能力;Annexin V-FITC/PI染色检测细胞凋亡情况;Transwell小室实验检测细胞迁移与侵袭能力;Western blot检测PI3K/AKT/mTOR信号通路相关蛋白的表达。结果胃肠道间质瘤组织中IGFBP-1阳性表达率高于癌旁组织(P<0.05);与空白对照组和siRNA-NC组比较,siRNA-IGFBP-1组细胞中IGFBP-1 mRNA和蛋白相对表达量均降低(均P<0.05);IGFBP-1沉默后细胞增殖活性下降,EDU阳性细胞率降低,凋亡率增加,迁移与侵袭细胞数目均减少(均P<0.05);p-PI3K/PI3K、p-AKT/AKT及p-mTOR/mTOR比值下降(均P<0.05)。结论沉默IGFBP-1表达可抑制胃肠道间质瘤细胞增殖、迁移与侵袭,并促进细胞凋亡,其机制可能与抑制PI3K/AKT/mTOR信号通路激活相关。ObjectiveTo investigate the expression of insulin-like growth factor binding protein 1(IGFBP-1)in human gastrointestinal stromal tumors,and its effect on the growth of gastrointestinal stromal tumor cells as well as its underlying mechanism.MethodsThe expression of IGFBP-1 was detected by immunohistochemical staining.The human gastrointestinal stromal tumor cells GIST882 were transfected with siRNA-NC(siRNA-NC group)and siRNA-IGFBP-1(siRNA-IGFBP-1 group),respectively,and blank control group was set.The mRNA and protein expression level of IGFBP-1 were detected by qRT-PCR and the Western blot;the cell viability was detected by the CCK-8 experiment;the cell proliferation ability was detected by the EDU test;the cell apoptosis was detected by Annexin V-FITC/PI staining;the cell migration and invasion ability was detected by Transwell chamber experiment,and the expression of PI3 K/AKT/mTOR signaling pathway-related proteins was detected by the Western blot.ResultsThe positive expression rate of IGFBP-1 in gastrointestinal stromal tumor tissues was higher than that in adjacent tissues(P<0.05).Compared with the blank control group and the siRNA-NC group,the relative expression of IGFBP-1 mRNA and protein in siRNA-IGFBP-1 group were decreased(all P<0.05).After IGFBP-1 silencing,the cell proliferation activity decreased,the EDU positive cells rate decreased,the apoptosis rate increased,and the number of migrating and invading cells decreased(both P<0.05);and the ratios of p-PI3 K/PI3 K,p-AKT/AKT and p-mTOR/mTOR decreased(all P<0.05).ConclusionsSilencing IGFBP-1 expression can inhibit the cell proliferation,migration,invasion of gastrointestinal stromal tumor,and promote cell apoptosis,which may be related to the inhibition of PI3 K/AKT/mTOR signal pathway activation.

关 键 词：胃肠道间质瘤 胰岛素样生长因子结合蛋白1 增殖 凋亡 迁移 侵袭 

分 类 号：R735.2[医药卫生—肿瘤]