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抗氧化干预对肝癌细胞增殖及N-ras基因表达的作用

Inhibition of Proliferation and Expression of N-ras in Hepatoma Cells by Antioxidation Treatment

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【作者】 刘珊林施冬云潘喜华申宗侯

【Author】 LIU Shan Lin * , SHI Dong Yun, PAN Xi Hua, SHEN Zong Hou ( Department of Biochemistry, Medical Center of Fudan University, Shanghai 200032, China )

【机构】 复旦大学医学院(原上海医科大学)生物化学教研室!上海200032

【摘要】 探讨了抗氧化剂抑制肿瘤块生长 ,促进癌细胞凋亡作用。在昆明小鼠皮下接种肝癌细胞悬液 ,同时灌服各种抗氧化剂维生素E、β胡萝卜素、谷氨酰胺、硒酸酯多糖、云芝多糖 ,有不同程度抑制肿瘤块生长作用 ,后两种多糖抗氧化剂具促进非特异性免疫能力提高和血浆中NO含量增高 ,并增强对肿瘤的抑制作用。在 772 1人肝癌细胞株中 ,加入以上各种抗氧化剂 ,能不同程度抑制癌细胞增殖并促使细胞凋亡 ,与此同时 ,小鼠血浆中谷胱甘肽过氧化物酶 (GSH Px)活力提高、丙二醛 (MDA)含量下降。低浓度过氧化氢可促进癌细胞增殖 ,高浓度可促使细胞凋亡或坏死。其可能的机制一是阻断自由基对癌细胞增殖的信号转导 ,抑制N ras癌基因表达 ;同时Mn SOD、c fos、c junmRNA表达提高。二是通过提高非特异性免疫能力促进NO释放 ,直接抑制癌细胞生长

【Abstract】 Kunming mice inoculated with hepatoma cell (H22) suspension subcutaneously at their right axilla were administered orally with antioxidants such as vitamine E, β carotene, glutamine, kappa selenocarrageenan and polysaccharide peptide of coriolus (PSP) solution. It was found that the inoculated hepatoma growth was suppressed to various extents. The two kinds of polysaccharide antioxidants improved non specific immunity, enhanced the nitrogen monoxide (NO) content in plasma and strengthened the inhibition of hepatoma. Above antioxidants added in the culture of 7721 human hepatoma cells inhibited the cell proliferation and induced its apoptosis. Meanwhile, the activity of glutathione peroxidase (GSH Px) in the plasma of mice increased and the content of malondialdehyde (MDA) decreased. H 2O 2 in low concentration improved the cancer cell proliferation and inhanced the expression of Mn SOD、 c fos and c jun , but led to cells apoptosis or necrosis in high concentration. The mechanism of antioxidants inhibiting tumor growth and improving cancer cells apoptosis might be that, on the one hand, the antioxidants blocked the free radicals signal transduction on cancer cells proliferation, and on the other hand, they improved the release of NO through enhancing the non specific immunity, so inhibiting the cancer cells proliferation directly.

【关键词】 抗氧化剂细胞凋亡NO人肝癌细胞株N-ras基因
【Key words】 antioxidantapoptosisNOhuman hepatoma cell strainN ras
【基金】 卫生部基金(No .98116 5 );上海市教委重点科研项目资助&&
  • 【文献出处】 生物化学与生物物理学报 ,Acta Biochimica Et Biophysica Sinica , 编辑部邮箱 ,2001年04期
  • 【分类号】Q78
  • 【被引频次】43
  • 【下载频次】243
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