创新抗肿瘤药物—乙烷硒啉对小鼠H22肝癌皮下移植瘤的氧化还原状态研究

创新抗肿瘤药物—乙烷硒啉对小鼠H22肝癌皮下移植瘤的氧化还原状态研究

王立辉, 曾慧慧^*

北京大学天然药物与仿生药物国家重点实验室, 北京 100191

收稿日期:2009-06-01 修回日期:2009-08-10 出版日期:2009-09-15 发布日期:2009-09-15
通讯作者: 曾慧慧*

Investigation of the redox status in H22 hepatocellular carcinoma xenografts treated by a novel anticancer drug——ethaselen

Li-Hui Wang^1,2, Hui-Hui Zeng^1,2*

1. State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China
2. Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China

Received:2009-06-01 Revised:2009-08-10 Online:2009-09-15 Published:2009-09-15
Contact: Hui-Hui Zeng*

摘要/Abstract

摘要：

我们研究了以硫氧还蛋白还原酶为靶点的创新抗肿瘤药物—乙烷硒啉在不同剂量下, 对小鼠H22 肝癌肿瘤组织中的氧化还原状态的影响。主要考察了小分子抗氧化物质谷胱甘肽(GSH), 脂质过氧化产物丙二醛(MDA)含量及重要的抗氧化物酶活性以反映H22肿瘤组织中的氧还状态。我们发现, GSH含量, 硫氧还蛋白还原酶和超氧化物歧化酶的活性的降低, 以及丙二醛含量的升高, 都和肿瘤生长抑制及乙烷硒啉的剂量密切相关。而谷胱甘肽还原酶以及谷胱甘肽过氧化物酶在一些药物剂量下, 有代偿性的活性上升趋势。过氧化氢酶几乎不受影响。最后, 我们研究了肿瘤生长抑制率与这些肿瘤氧还因子的关系。我们的研究显示: 乙烷硒啉可能是通过诱导氧化应激水平抑制小鼠体内H22肿瘤细胞的生长。

关键词: 乙烷硒啉, 硫氧还蛋白还原酶, 抗癌药物, 氧化还原态, 抗氧化系统, 肝细胞癌

Abstract:

We investigated the redox status of H22 hepatocellular carcinoma xenografts treated with various doses of ethaselen, a novel anticancer drug targeting thioredoxin reductase (TrxR). The concentrations of low molecular weight antioxidant glutathione (GSH) and malondialdehyde (MDA), a product of lipid peroxidation, as well as the activities of important antioxidant enzymes were measured for elucidating the redox status of H22 tumor tissues. We found that the decreased GSH level, decreased thioredoxin reductase and superoxide dismutase (SOD) activities as well as increased MDA content were closely related to the tumor growth inhibition and ethaselen doses. Glutathione peroxidase (GPx) and glutathione reductase (GR) activities are also affected by ethaselen treatment. However, the catalase (CAT) activity remains unchanged. Finally, we studied the relationship of tumor growth inhibition caused by ethaselen with these redox factors. This study showed that ethaselen could elevate the oxidative stress to suppress the H22 tumor growth in mice model.

Key words: Ethaselen, Ethaselen, Thioredoxin reductase inhibitor, Thioredoxin reductase inhibitor, Anticancer drug, Anticancer drug, Redox status, Redox status, Antioxidant system, Antioxidant system, Hepatocellular carcinoma, Hepatocellular carcinoma

中图分类号:

R969.1

Supporting:

Foundation item: National Natural Science Foundation of China (Grant No. 30472036).
^*Corresponding author. Tel.: 86-10-82802878; e-mail: zenghh@bjmu.edu.cn

王立辉, 曾慧慧^*. 创新抗肿瘤药物—乙烷硒啉对小鼠H22肝癌皮下移植瘤的氧化还原状态研究[J]. .

Li-Hui Wang^1,2, Hui-Hui Zeng^1,2* . Investigation of the redox status in H22 hepatocellular carcinoma xenografts treated by a novel anticancer drug——ethaselen[J]. .

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