1α,25-二羟基维生素D3抑制人结肠癌细胞系SW480中β-catenin转录活性

基础医学与临床 ›› 2020, Vol. 40 ›› Issue (9): 1169-1174.

• 研究论文 • 下一篇

1α,25-二羟基维生素D₃抑制人结肠癌细胞系SW480中β-catenin转录活性

辛玉¹, 贺龙梅², 杨红¹, 吕红¹, 谭蓓¹, 汪红英^2*, 钱家鸣^1*

1.中国医学科学院北京协和医学院北京协和医院消化内科,北京 100730;
2.中国医学科学院北京协和医学院肿瘤医院国家癌症中心国家肿瘤临床医学研究中心,北京 100021

收稿日期:2019-08-26 修回日期:2020-01-03 出版日期:2020-09-05 发布日期:2020-09-04
通讯作者: ^*qianjiaming1957@126.com;hongyingwang@cicams.ac.cn
基金资助:
国家自然科学基金(81570505);山东省自然科学基金(ZR2019PH081);山东省重点研发计划(2017G006030)

1α,25-Dihydroxyvitamin D₃ inhibits β-catenin transcriptional activity in human colon cancer cell line SW480

XIN Yu¹, HE Long-mei², YANG Hong¹, LYU Hong¹, TAN Bei¹, WANG Hong-ying^2*, QIAN Jia-ming^1*

1. Department of Gastroenterology, Peking Union Medical College Hospital, CAMS ＆ PUMC, Beijing 100730;
2. National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, CAMS ＆ PUMC, Beijing 100021, China

Received:2019-08-26 Revised:2020-01-03 Online:2020-09-05 Published:2020-09-04
Contact: ^*qianjiaming1957@126.com;hongyingwang@cicams.ac.cn

摘要/Abstract

摘要： 目的探讨1α,25-二羟基维生素D₃[1,25(OH)₂D₃]对人结肠癌细胞系SW480中β-catenin转录活性的影响及作用机制。方法 1,25(OH)₂D₃(100 nmol/L)干预和溶剂对照处理SW480细胞48 h;用双荧光素酶报告系统检测β-catenin的转录活性;Western blot检测1,25(OH)₂D₃干预后β-catenin在细胞核/质内的定位变化;用RT-qPCR和Western blot检测β-catenin和FOXM1 mRNA及蛋白水平。采用siRNA敲降SW480细胞中FOXM1后,检测1,25(OH)₂D₃干预后β-catenin转录活性的变化。结果 1)在SW480细胞中,1,25(OH)₂D₃能显著降低β-catenin的转录活性(P＜0.05),但不影响β-catenin mRNA和蛋白表达水平; 2)1,25(OH)₂D₃上调SW480细胞中FOXM1蛋白水平的表达(P＜0.05); 3)敲降SW480细胞中FOXM1降低1,25(OH)₂D₃对β-catenin转录活性的抑制作用(P＜0.05)。结论 1,25(OH)₂D₃通过上调FOXM1的表达,发挥抑制β-catenin转录活性的作用。

关键词: 1α,25-二羟基维生素D₃, 结肠癌, β-catenin, FOXM1

Abstract: Objective To explore the inhibitory effect and mechanism of 1α,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃]on β-catenin transcriptional activity in human colon cancer cells. Methods Colon cancer cell line SW480 was treated with either 1,25(OH)₂D₃ (100 nmol/L) or vehicle (control) for 48 hours, then several parameters were measured: the transcriptional activity of β-catenin by Dual-Luciferase? Reporter Assay System; the nuclear protein expression level of β-catenin by Western blot; mRNA coding for β-catenin and forkhead box M1 (FOXM1) and the protein expression by RT-qPCR and Western blot. SW480 cells were subjected to transfecting siRNA to knock down FOXM1, followed by 1,25(OH)₂D₃ treatment and measurement of the transcriptional activity of β-catenin by Dual-Luciferase? Reporter Assay System. Results 1) 1,25(OH)₂D₃ significantly repressed the transcriptional activity of β-catenin in SW480 cells (P＜0.05), while did not affect its mRNA and protein expression; 2)1,25(OH)₂D₃ increased the protein expression of FOXM1(P＜0.05); 3)The inhibitory effect of the transcriptional activity of β-catenin by 1,25(OH)₂D₃ in SW480 cells was decreased when FOXM1 was knocked down(P＜0.05). Conclusions 1,25(OH)₂D₃ represses the transcriptional activity of β-catenin via increasing FOXM1 expression.

Key words: 1,25(OH)₂D₃, colon cancer, β-catenin, FOXM1

中图分类号:

R574.62

辛玉, 贺龙梅, 杨红, 吕红, 谭蓓, 汪红英, 钱家鸣. 1α,25-二羟基维生素D₃抑制人结肠癌细胞系SW480中β-catenin转录活性[J]. 基础医学与临床, 2020, 40(9): 1169-1174.

XIN Yu, HE Long-mei, YANG Hong, LYU Hong, TAN Bei, WANG Hong-ying, QIAN Jia-ming. 1α,25-Dihydroxyvitamin D₃ inhibits β-catenin transcriptional activity in human colon cancer cell line SW480[J]. Basic & Clinical Medicine, 2020, 40(9): 1169-1174.

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1α,25-二羟基维生素D₃抑制人结肠癌细胞系SW480中β-catenin转录活性

1α,25-Dihydroxyvitamin D₃ inhibits β-catenin transcriptional activity in human colon cancer cell line SW480

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