18β-甘草次酸通过Wnt/β-catenin信号通路对U937细胞凋亡的调控机制研究

吴晓玲,庄佩佩,郝嘉楠,邓光存*

中国药学杂志 ›› 2014, Vol. 49 ›› Issue (19) : 1710-1715.

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中国药学杂志 ›› 2014, Vol. 49 ›› Issue (19) : 1710-1715. DOI: 10.11669/cpj.2014.19.009
论 著

18β-甘草次酸通过Wnt/β-catenin信号通路对U937细胞凋亡的调控机制研究

  • 吴晓玲,庄佩佩,郝嘉楠,邓光存*
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Regulation of 18β-Glycyrrhetinic Acid on Apoptosis of U937 Cell through Activation of Wnt/β-Catenin Signal

  • WU Xiao-ling, ZHUANG Pei-pei, HAO Jia-nan, DENG Guang-cun*
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摘要

目的 探讨18β-甘草次酸(GA)通过Wnt/β-catenin信号对人类白血病细胞株U937细胞凋亡的调控机制。方法 用双荧光素酶报告基因检测Wnt经典信号通路信号,用四甲基偶氮唑蓝法检测细胞增殖,Annex in V /PI双标法检测凋亡率及坏死率,Western-blot检测凋亡及坏死相关蛋白水平。结果 18β-甘草次酸能增强Wnt/β-catenin信号通路的β-catenin/TCF活性,从而上调该信号通路靶蛋白CyclinD1的表达;并通过上调促凋亡蛋白BAX的表达,下调抗凋亡蛋白Mcl-1、Bcl-2和坏死蛋白RIP3的蛋白表达水平,同时增强caspase3活性,从而诱导细胞凋亡,且在一定范围内呈剂量依赖性。结论 18β-甘草次酸通过激活Wnt/β-catenin信号通路来抑制U937细胞增殖和诱导其凋亡,并且对细胞的坏死没有促进作用。

Abstract

OBJECTIVE To explore the regulation of 18β-glycyrrhetinic acid on apoptosis of human acute leukemia U937 cell through Wnt/β-catenin signal. METHODS Wnt/β-catenin signal was assessed with a dual luciferase reporter assay; cell proliferation was determined with MTT,apoptosis and necrosis rate was detected by AnnexinV-FITC/ PI double staining, Western-blot was used to analyse the expression of related protein. RESULTS 18β-Glycyrrhetinic acid can activate the wnt/β-catenin signal with increasing β-catenin/TCF activity and the expressing of CyclinD 1. Meanwhile up-regulate the expressing of BAX, down-regulating expressing of Mcl-1,Bcl-2 and RIP3, inhibitting the proliferation and enhancing the activity of caspase 3 in a dose-dependent manner in certain range. CONCULSION 18β-Glycyrrhetinic acid can promote apoptosis and not induce necrosis of human acute leukemia U937 cell through activation of Wnt/β-catenin signal.

关键词

U937细胞 / 18β-甘草次酸 / 凋亡 / Wnt经典信号通路

Key words

U937 cells / 18β-glycyrrhetinic acid / apoptosis / Wnt/β-catenin signal

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吴晓玲,庄佩佩,郝嘉楠,邓光存*. 18β-甘草次酸通过Wnt/β-catenin信号通路对U937细胞凋亡的调控机制研究[J]. 中国药学杂志, 2014, 49(19): 1710-1715 https://doi.org/10.11669/cpj.2014.19.009
WU Xiao-ling, ZHUANG Pei-pei, HAO Jia-nan, DENG Guang-cun*. Regulation of 18β-Glycyrrhetinic Acid on Apoptosis of U937 Cell through Activation of Wnt/β-Catenin Signal[J]. Chinese Pharmaceutical Journal, 2014, 49(19): 1710-1715 https://doi.org/10.11669/cpj.2014.19.009
中图分类号: R965   

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基金

国家自然科学基金资助项目(31460301)
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