沉默牛磺酸上调基因1通过Wnt/CTNNB1信号通路提高胃癌细胞对顺铂和5-氟尿嘧啶的敏感性  

Taurine upregulated gene 1 silencing enhances the sensitivity of gastric cancer cells to cisplatin and 5-fluorouracil through the Wnt/CTNNB1 signaling pathway

作　　者：关国欣[1] 王冰[2] 黄宝俊[3] 赵丹懿[2] GUAN Guoxin;WANG Bing;HUANG Baojun;ZHAO Danyi(Department of Emergency Abdominal Surgery,The Second Hospital of Dalian Medical University,Dalian 116027,China;Department of Oncology,The Second Hospital of Dalian Medical University,Dalian 116027,China;Department of Surgical Oncology,The First Hospital,China Medical University,Shenyang 110001,China)

机构地区：[1]大连医科大学附属第二医院急腹症外科,辽宁大连116027 [2]大连医科大学附属第二医院肿瘤科,辽宁大连116027 [3]中国医科大学附属第一医院肿瘤外科,沈阳110001

出　　处：《中国医科大学学报》2020年第12期1061-1065,1081,共6页Journal of China Medical University

基　　金：国家自然科学基金(81272716)。

摘　　要：目的探讨牛磺酸上调基因1(TUG1)调控胃癌细胞对顺铂(CDDP)和5-氟尿嘧啶(5-FU)敏感性的作用效果及机制。方法实时定量PCR法检测TUG1在CDDP和5-FU耐药的胃癌组织和细胞系(SGC7901/R)中的表达。应用增强型CCK8法检测细胞的增殖活力,并计算CDDP和5-FU的半抑制浓度(IC50)。双荧光素酶实验检测Wnt/CTNNB1信号通路活性。Western boltting检测CTNNB1蛋白的表达。结果与对照组胃癌组织和细胞系(SGC7901)相比,TUG1在CDDP和5-FU耐药的胃癌组织和细胞系(SGC7901/R)中高表达。TUG1沉默上调了SGC7901/R细胞中CDDP和5-FU的IC50,提高了化疗敏感性。TUG1沉默降低了SGC7901/R细胞中Wnt/CTNNB1信号通路的活性,并抑制了CTNNB1蛋白的表达。CTNNB1过表达激活了SGC7901/R细胞中Wnt/CTNNB1信号通路,逆转了TUG1沉默对CDDP和5-FU化疗敏感性的促进作用。结论TUG1与胃癌的化疗不敏感相关,沉默TUG1通过Wnt/CTNNB1信号通路提高胃癌细胞对CDDP和5-FU的敏感性。Objective To explore the effect and mechanism of taurine upregulated gene 1(TUG1)on the sensitivity of gastric cancer(GC)cells to cisplatin(CDDP)and 5-fluorouracil(5-FU).Methods The expression of TUG1 in CDDP-and 5-FU-resistant GC tissues and SGC7901/R cells was detected by real-time quantitative PCR.Cell proliferation was measured using the enhanced CCK8 assay.The half maximal inhibitory concentration(IC50)of CDDP and 5-FU were calculated.The activity of Wnt/CTNNB1 signaling pathway was detected by the double luciferase assay.Western blotting was used to detect CTNNB1 protein expression.Results Compared with control GC tissues and SGC7901 cells,TUG1 was highly expressed in CDDP and 5-FU resistant GC tissues and SGC7901/R cells.TUG1 silencing increased the IC50 of CDDP and 5-FU in SGC7901/R cells and enhanced their chemosensitivity.TUG1 silencing inactivated the Wnt/CTNNB1 signaling pathway and inhibited CTNNB1 protein expression in SGC7901/R cells.CTNNB1 protein overexpression activated the Wnt/CTNNB1 signaling pathway in SGC7901/R cells and reversed the promoting effects of TUG1 silencing on the chemosensitivity of the cells to CDDP and 5-FU.Conclusion TUG1 is related to chemotherapy insensitivity in GC.TUG1 silencing enhances the sensitivity of GC cells to CDDP and 5-FU through the Wnt/CTNNB1 signaling pathway.

关 键 词：胃癌 牛磺酸上调基因1 Wnt/CTNNB1信号通路 化学治疗 

分 类 号：R735.2[医药卫生—肿瘤]