Doxorubicin resistance conferred by selective enhancement of intracellular glutathione peroxidase or superoxide dismutase content in human MCF-7 breast cancer cells.
Doxorubicin resistance conferred by selective enhancement of intracellular glutathione peroxidase or superoxide dismutase content in human MCF-7 breast cancer cells.
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DOI：
10.3109/10715769109145859
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
J. Doroshow;S. Akman;S. Esworthy;Fong-Fong Chu-Fong;T. Burke
中科院分区：
文献类型：
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作者：
J. Doroshow;S. Akman;S. Esworthy;Fong-Fong Chu-Fong;T. Burke
为了研究阿霉素刺激的氧自由基形成在肿瘤细胞杀伤中的作用，我们通过“刮擦加载”将谷胱甘肽过氧化物酶 (GSH Px) 或超氧化物歧化酶 (SOD) 引入 MCF-7 细胞中。用 150 或 300 单位/ml 的 GSH Px 或 20 或 40 单位/ml 处理后，对照细胞质 GSH Px 和 SOD 水平分别从（平均值 +/- S.E.）0.37 nmol/min/mg 和 0.58 微克 SOD/mg 增加至 3.99 或 7.63 nmol/min/mg 和 1.40 或 1.83 微克 SOD/mg毫克/毫升 SOD。对阿霉素的耐药性与引入 MCF-7 细胞的 GSH Px 水平相关；暴露于 1.75 microM 多柔比星一小时，仅加载培养基的对照细胞的克隆效率降低至 34%，而用 150 或 300 单位/ml GSH Px 增强的多柔比星处理细胞的铺板效率为 56 或 86%，P 小于 0.05。 SOD 的引入同样增加了 MCF-7 对阿霉素的抗性。热灭活的酶没有保护作用。负载 GSH Px 的细胞也对氧化还原循环抗癌醌丝裂霉素 C 具有抗性，但对氧化还原无活性类似物 5-亚氨基道诺红霉素和米托蒽醌没有抗性，这表明 GSH Px 或 SOD 水平的扩增可以在 MCF-7 细胞中产生阿霉素抗性。
To examine the role of doxorubicin-stimulated oxyradical formation in tumor cell killing, we introduced glutathione peroxidase (GSH Px) or superoxide dismutase (SOD) into MCF-7 cells by "scrape loading." Control cytoplasmic GSH Px and SOD levels increased from (mean +/- S.E.) 0.37 nmol/min/mg and 0.58 microgram SOD/mg, respectively, to 3.99 or 7.63 nmol/min/mg and 1.40 or 1.83 micrograms SOD/mg after treatment with either 150 or 300 units/ml of GSH Px or 20 or 40 mg/ml SOD. Resistance to doxorubicin was correlated with the level of GSH Px introduced into the MCF-7 cells; a one-hour exposure to 1.75 microM doxorubicin decreased the cloning efficiency of control cells loaded with medium alone to 34%, whereas doxorubicin-treated cells augmented with 150 or 300 units/ml of GSH Px had plating efficiencies of 56 or 86%, P less than 0.05. Introduction of SOD increased MCF-7 resistance to doxorubicin similarly. The heat-inactivated enzymes were not protective. Cells loaded with GSH Px were also resistant to the redox cycling anticancer quinone mitomycin C but not to the redox inactive analogs 5-iminodaunorubicin and mitoxantrone, suggesting that amplification of GSH Px or SOD levels can produce doxorubicin resistance in MCF-7 cells.