rBTI induces apoptosis in human solid tumor cell lines by loss in mitochondrial transmembrane potential and caspase activation
rBTI induces apoptosis in human solid tumor cell lines by loss in mitochondrial transmembrane potential and caspase activation
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rBTI 通过线粒体跨膜电位损失和 caspase 激活诱导人实体瘤细胞系凋亡
DOI：
10.1016/j.toxlet.2009.05.018
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发表时间：
2009-09-10
影响因子：
3.5
通讯作者：
Zhu, Lei
中科院分区：
文献类型：
--
作者：
Li, Yu-Ying;Zhang, Zheng;Zhu, Lei
研究了重组荞麦胰蛋白酶抑制剂（rBTI）诱导人实体瘤细胞（EC9706、HepG2和HeLa）凋亡的分子机制及其可能的作用。MTT实验表明，rBTI能特异性抑制实体瘤细胞的生长，且具有密切的时间依赖性。流式细胞术分析显示，rBTI在6.25 ~ 50 μ g/ml范围内增加了几种肿瘤细胞的凋亡。DNA电泳分析显示“DNA阶梯”，是细胞凋亡的典型特征。rbti诱导的细胞凋亡涉及Bax和Bak上调，Bcl-2和Bcl-xl下调，细胞色素c从线粒体向细胞质释放，caspase-3和-9的激活以及线粒体跨膜电位的破坏（δ psi(m)）。z-DEVD-fmk caspase-3抑制剂显著抑制rbti诱导的细胞凋亡。结果表明，rBTI可诱导多种实体瘤细胞凋亡，并通过线粒体凋亡途径促进细胞凋亡。2009爱思唯尔爱尔兰有限公司版权所有。
The molecular mechanisms and the possible effects of a recombinant buckwheat trypsin inhibitor (rBTI) on the induction of apoptosis in the human solid tumor cells (EC9706, HepG2 and HeLa) were investigated. An MTT assay showed that rBTI could specifically inhibit the growth of solid tumor cells in a close- and time-dependent manner. Analysis by flow cytometry indicated that the apoptosis of several tumor cells increased after treatment with rBTI in range of 6.25-50 mu g/ml. DNA electrophoresis analysis showed the 'DNA ladder', typical of apoptosis. rBTI-induced apoptosis was shown to involve Bax and Bak up-regulation, Bcl-2 and Bcl-xl down-regulation, release of cytochrome c from the mitochondria to the cytosol, activation of caspase-3 and -9 and disruption of the mitochondrial transmembrane potential (Delta psi(m)). The z-DEVD-fmk caspase-3 inhibitor significantly inhibited rBTI-induced apoptosis. We concluded that rBTI can induce the apoptosis in several types of human solid tumor cells and promotes apoptosis through the mitochondrial apoptotic pathway. (C) 2009 Elsevier Ireland Ltd. All rights reserved.