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。

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

关国欣¹, 王冰², 黄宝俊³, 赵丹懿²

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

收稿日期:2020-01-18出版日期:2020-12-30发布日期:2020-12-09
通讯作者:赵丹懿E-mail:zhaodanyi@dlmedu.edu.cn
作者简介:关国欣(1978-),男,副主任医师,博士.
基金资助:国家自然科学基金（81272716）


关键词: 胃癌, 牛磺酸上调基因1, Wnt/CTNNB1信号通路, 化学治疗
Abstract: 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.
Key words: gastric cancer, taurine up-regulated 1, Wnt/CTNNB1 signaling pathway, chemotherapy
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