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从狝猴桃根中分离得到的CRA(熊果酸)通过下调NF-κB通路在体外诱导人胃癌细胞系BGC823凋亡。

CRA(Crosolic Acid) isolated from Actinidia valvata Dunn.Radix induces apoptosis of human gastric cancer cell line BGC823 in vitro via down-regulation of the NF-κB pathway.

作者信息

Cheng Qi-Lai, Li Hong-Liang, Li Ying-Chen, Liu Zhao-Wen, Guo Xiao-Hua, Cheng Yi-Jian

机构信息

College of Pharmacy, Gannan Medical University, Ganzhou 341000, Jiangxi Province, PR China.

Post-doctoral Research Station of Clinical Medicine, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, PR China.

出版信息

Food Chem Toxicol. 2017 Jul;105:475-485. doi: 10.1016/j.fct.2017.05.021. Epub 2017 May 12.

Abstract

A natural ursolic compound, 2α,3β-dihydroxy-urs-12-en-28-oic acid (corosolic acid, CRA) was isolated from the root of Actinidia valvata Dunn. (A. valvata Radix). Since a large number of triterpenoid compound has marked anticancer effects toward various types of cancer cell lines in vitro, this study was carried out to investigate the anticancer effect of CRA in human gastric cancer cell line BGC823 cells and the underlying apoptotic mechanism of CRA was examined in BGC823 cell lines. The results showed that CRA significantly suppressed the viability of BGC823 cells in a concentration- and time-dependent manner. CRA also significantly increased the sub G1 population by cell cycle analysis in a concentration dependent manner. Exposure to CRA decreased p65, bcl-2, Fas, smac mRNA and protein expression, and increased IκBα, bax, survivin mRNA and protein expression. Results of immunofluorescence staining and EMSA further indicated CRA induced apoptosis by inhibiting nuclear translocation of nuclear factor NF-κB subunit p65. Consistently overall, our findings suggest that CRA induces apoptosis via inhibition of NF-κB (p65) expression level and activation of IκBα in BGC cells as a potent anticancer candidate for gastric cancer treatment.

摘要

从狝猴桃根(狝猴桃根)中分离出一种天然熊果酸类化合物,2α,3β - 二羟基 - 乌苏 - 12 - 烯 - 28 - 酸(科罗索酸,CRA)。由于大量三萜类化合物在体外对多种癌细胞系具有显著的抗癌作用,本研究旨在探讨CRA对人胃癌细胞系BGC823细胞的抗癌作用,并在BGC823细胞系中研究CRA潜在的凋亡机制。结果表明,CRA以浓度和时间依赖性方式显著抑制BGC823细胞的活力。通过细胞周期分析,CRA还以浓度依赖性方式显著增加亚G1期细胞比例。暴露于CRA可降低p65、bcl - 2、Fas、smac mRNA和蛋白表达,并增加IκBα、bax、survivin mRNA和蛋白表达。免疫荧光染色和电泳迁移率变动分析结果进一步表明,CRA通过抑制核因子NF - κB亚基p65的核转位诱导细胞凋亡。总体而言,我们的研究结果一致表明,CRA通过抑制BGC细胞中NF - κB(p65)表达水平和激活IκBα诱导细胞凋亡,作为胃癌治疗的一种有效的抗癌候选物。

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