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过氧化氢促进氯化钆诱导HepG2细胞凋亡

Hydrogen peroxide promotes gadolinium-induced apoptosis of HepG2 cells

中文摘要英文摘要

稀土钆抗癌化合物一直是稀土药用研究的热点之一。在钆化合物抗癌作用机制中,由于钆通常降低细胞活性氧物种(ROS)水平,使ROS的意义扑朔迷离。本文研究过氧化氢对氯化钆诱导HepG2细胞凋亡的影响。结果显示,过氧化氢能够显著促进钆离子诱导细胞凋亡;用Western Blot检测凋亡相关蛋白,发现过氧化氢与钆离子共同作用时,可导致明显的PARP剪切,但对凋亡相关MAPK以及线粒体信号通路的激活较两者单独作用都弱;溶液中过氧化氢和钆离子共同作用可导致小牛胸腺DNA的断裂损伤。因此,上述结果表明过氧化氢促进钆离子杀伤HepG2肿瘤细胞的机制不是通过增强钆离子启动的细胞信号实现,而可能是两者共同作用造成对DNA的损伤所致,这为抗肿瘤稀土化合物研究提供了新的思路,有关化学和分子生物学机制值得深入的研究。

nticancer gadolinium compounds are of great interest in the studies of medical applications of lanthanides. Investigations on the mechanisms of anticancer actions of gadolinium compounds revealed that gadolinium decreased the levels of reactive oxygen species (ROS) in cancer cells, which is inconsistent with the current view of ROS in cell apoptosis. The present work investigated the roles of hydrogen peroxide on gadolinium induced apoptosis of HepG2 cancer cell line. The experimental results revealed that hydrogen peroxide promote gadolinium-induced HepG2 apoptosis. Analyses of apoptotic relevant proteins with Western Blot indicated that incubation of cells with Gd(III) ions and hydrogen peroxide results in significant cleavage PARP proteins but caused much weaker effects on MAPK or mitochondrial apoptotic signal transduction. Meanwhile, Gd(III) ions and hydrogen peroxide could cause fragmentations of calf thymus DNA. All these results suggested that instead of enhancing Gd-induced cellular signal, hydrogen peroxide promotes HepG2 apoptosis by increasing Gd-induced DNA damages. Further works into the mechanisms would be appropriate, nevertheless, this mechanism may provide new insight for design and discovery of anticaner lanthanide compounds.

刘会雪、王夔、叶丽华、杨晓达

基础医学生物化学分子生物学

氯化钆过氧化氢细胞凋亡癌症HepG2

Gadoliniumhydrogen perxideapoptosiscancerHepG2

刘会雪,王夔,叶丽华,杨晓达.过氧化氢促进氯化钆诱导HepG2细胞凋亡[EB/OL].(2012-06-21)[2025-05-04].http://www.paper.edu.cn/releasepaper/content/201206-305.点此复制

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