核受体Nurr1对胃癌细胞5-氟尿嘧啶耐药性的影响和机制研究  

Effect and mechanism syudy of nuclear receptor Nurr1 on 5-Fluorouracil drug resistance of gastric cancer cells

作　　者：曾珊 周捷[1] 黄红兵[1] 刘韬[1] 王汉渝[1] 殷淑文 ZENG Shan;ZHOU Jie;HUANG Hongbing(Pharmacy department of Sun Yat-sen University Cancer Center,State Key Laboratory of Oncology in South China,Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy,Guangzhou 510060,China)

机构地区：[1]中山大学肿瘤防治中心药学部/华南恶性肿瘤防治全国重点实验室/广东省鼻咽癌诊治研究重点实验室,广州510060

出　　处：《中国处方药》2024年第12期44-48,共5页Journal of China Prescription Drug

摘　　要：目的研究核受体Nurr1对胃癌细胞5-氟尿嘧啶(5-FU)耐药性的影响和机制。方法应用慢病毒载体转染人胃癌细胞SGC-7901和5-FU耐药胃癌细胞SGC-7901/5-FU,构建过表达和低表达Nurr1的稳定细胞系,按不同实验细胞设6个组别进行研究:对照组、Nurr1过表达组、Nurr1低表达组、耐药对照组、耐药Nurr1过表达组、耐药Nurr1低表达组,各组均加入终浓度为5μg/ml的5-FU处理24 h,以CCK-8法检测各组细胞的存活率,流式细胞法检测细胞凋亡率,蛋白印迹法(WB)检测Nurr1、Bax、Bcl-2、p53的表达量。结果在5μg/ml 5-FU的作用下,细胞凋亡率依次为Nurr1过表达组<对照组<Nurr1低表达组,耐药Nurr1过表达组<耐药对照组<耐药Nurr1低表达组;Nurr1、Bcl-2表达量依次为Nurr1过表达组>对照组>Nurr1低表达组,耐药Nurr1过表达组>耐药对照组>耐药Nurr1低表达组;Bax、p53表达量均依次为Nurr1过表达组<对照组<Nurr1低表达组,耐药Nurr1过表达组<耐药对照组<耐药Nurr1低表达组。结论Nurr1的表达量与胃癌细胞对5-FU的耐药性密切相关,Nurr1可能通过调控Bax、Bcl-2、p53的表达水平影响胃癌细胞对5-FU的敏感性。Objective To study the effect and mechanism of nuclear receptor Nurr1 on 5-Fluorouracil(5-FU)drug resistance of gastric cancer cells.Methods Lentiviral vectors were applied to transfect human gastric cancer cells SGC-7901 and 5-FU drug-resistant gastric cancer cells SGC-7901/5-FU to construct stable cell lines with over-expression and low expression of Nurr1.Six groups were set up according to different experimental cells:control group,Nurr1 high expression group,Nurr1 low expression group group,5-FU resistant control group,5-FU resistant Nurr1 high expression group,5-FU resistant Nurr1 low expression group.The 5μg/ml concentration of 5-FU was added to each group for 24 hours,and CCK-8 method was used to detect cell survival rate,flow cytometry was used to detect apoptosis rate.The expression of Nurr1,Bax,Bcl-2 and p53 were detected by WB.Results At 5μg/ml 5-FU,the apoptosis rate of cell was in the order of Nurr1 high expression group<control group<Nurr1 low expression group,5-FU resistant Nurr1 high expression group<5-FU resistant control group<5-FU resistant Nurr1 low expression group.The expression levels of Bcl-2 and Nurr1 were in the following order:Nurr1 high expression group>control group>Nurr1 low expression group,5-FU resistant Nurr1 high expression group>5-FU resistant control group>5-FU resistant Nurr1 low expression group.The expression levels of Bax and p53 expression level was in the following order:Nurr1 high expression group<control group<Nurr1 low expression group,5-FU resistant Nurr1 high expression group<5-FU resistant control group<5-FU resistant Nurr1 low expression group.Conclusion The expression of Nurr1 was closely related to the resistance of gastric cancer cells to 5-FU.Nurr1 may affect the sensitivity of gastric cancer cells to 5-FU by regulating the expression levels of Bax,Bcl-2 and p53.

关 键 词：核受体 NURR1 胃癌 5-氟尿嘧啶 耐药性 

分 类 号：R735.2[医药卫生—肿瘤]