Honokiol inhibits HespG2 migration via down-regulation of IQGAP1 expression discovered by a quantitative pharmaceutical proteomic analysis
Honokiol inhibits HespG2 migration via down-regulation of IQGAP1 expression discovered by a quantitative pharmaceutical proteomic analysis
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定量药物蛋白质组学分析发现和厚朴酚通过下调 IQGAP1 表达来抑制 HespG2 迁移
DOI：
10.1002/pmic.200900649
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发表时间：
2010-04-01
期刊：
影响因子：
3.4
通讯作者：
Chen, Lijuan
中科院分区：
文献类型：
--
作者：
Liang, Shufang;Fu, Afu;Chen, Lijuan
厚朴酚（HNK）是一种天然小分子化合物，能抑制HepG 2细胞的增殖，并在裸鼠体内表现出抗肿瘤活性。本文应用一种新的基于细胞培养的氨基酸稳定同位素标记的定量蛋白质组学方法和裸鼠模型研究HNK与热点迁移分子Ras GTP酶激活样蛋白（IQGAP 1）的相关性。定量蛋白质组学分析显示，IQGAP 1在10 μ g/mL HNK作用24 h后下调0.53倍。HepG 2细胞在HNK作用下的迁移能力与IQGAP 1的表达水平相关。此外，在HepG 2细胞和肿瘤异种移植模型上的生化验证进一步证明HNK降低IQGAP 1及其上游蛋白Cdc 42/Rac 1的表达水平。这些数据支持HNK通过IQGAP 1与其上游Cdc 42/Rac 1蛋白相互作用，作用于Cdc 42/Rac 1信号通路，调节细胞粘附和细胞迁移，这是HNK发挥抗肿瘤活性的一种新的分子机制。
Honokiol (HNK), a natural small molecular product, inhibited proliferation of HepG2 cells and exhibited anti-tumor activity in nude mice. In this article, we applied a novel sensitive stable isotope labeling with amino acids in cell culture-based quantitative proteomic method and a model of nude mice to investigate the correlation between HNK and the hotspot migration molecule Ras GTPase-activating-like protein (IQGAP1). The quantitative proteomic analysis showed that IQGAP1 was 0.53-fold down-regulated under 10 mu g/mL HNK exposure for 24 h on HepG2 cells. Migration ability of HepG2 cells under HNK treatment was correlated with its expression level of IQGAP1. In addition, the biochemical validation on HepG2 cells and the tumor xenograft model further demonstrated that HNK decreased the expression level of IQGAP1 and its upstream proteins Cdc42/Rac1. These data supported that HNK can modulate cell adhesion and cell migration by acting on Cdc42/Rac1 signaling via IQGAP1 interactions with its upstream Cdc42/Rac1 proteins, which is a new molecular mechanism of HNK to exert its anti-tumor activity.