Role of lipid peroxidation and antioxidant enzymes in omega 3 fatty acids induced suppression of breast cancer xenograft growth in mice.
Role of lipid peroxidation and antioxidant enzymes in omega 3 fatty acids induced suppression of breast cancer xenograft growth in mice.
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DOI：
10.1186/1475-2867-2-10
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发表时间：
2002-07-17
影响因子：
5.8
通讯作者：
Cameron IL
中科院分区：
文献类型：
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作者：
Hardman WE;Munoz J Jr;Cameron IL
向小鼠补充高水平的膳食n-3多不饱和脂肪酸（PUFA）会增加细胞膜中的n-3 PUFA，增加细胞对脂质过氧化（LPO）的敏感性，并降低乳腺和其他肿瘤的生长速度。然而，早期研究的结果表明，除LPO外，一种因子也参与了n-3 PUFA喂养小鼠肿瘤生长的减少。给携带MDA-MB-231人乳腺癌异种移植物的无胸腺小鼠喂食鱼油浓缩物（FOC）或对照饮食，补充或不补充维生素E（2000 IU /kg饮食），并在多柔比星（DOX）处理之前和之后处死，以评价涉及肿瘤生长抑制的因素。在DOX之前，3%FOC喂养的小鼠的肿瘤中的基础LPO略高于对照喂养的小鼠，并且在食用FOC和维生素E的小鼠中降低。维生素E抑制对照小鼠肿瘤中DOX诱导的LPO增加，然而，维生素E不足以抑制FOC喂养小鼠肿瘤中DOX诱导的LPO增加。FOC喂养的小鼠的肿瘤的平均生长速率显著低于对照小鼠的肿瘤的平均生长速率。多元回归分析表明，抑制谷胱甘肽过氧化物酶（GPX）活性的FOC前DOX治疗是更重要的比增加LPO作为肿瘤生长抑制的解释。小鼠服用FOC后，肿瘤诱导的恶病质减少。似乎对DOX的敏感性增加与FOC诱导的GPX活性降低有关。FOC减少肿瘤诱导的恶病质。
Supplementing mice with high levels of dietary n-3 polyunsaturated fatty acids (PUFAs) increases the n-3 PUFAs in cell membranes, increases the susceptibility of the cells for lipid peroxidation (LPO) and decreases the growth rate of mammary and other tumors. However, the results of an earlier study indicated that a factor in addition to LPO was involved in the reduction in tumor growth in n-3 PUFAs fed mice. Athymic mice bearing MDA-MB-231 human breast carcinoma xenografts, were fed fish oil concentrate (FOC) or control diets, with and without supplemental Vitamin E (2000 IU /kg diet) and were sacrificed both before and after doxorubicin (DOX) treatment to evaluate factors involved in tumor growth suppression. Prior to DOX, basal LPO in the tumor of 3% FOC fed mice was slightly higher than in the control fed mice and was decreased in mice consuming FOC with vitamin E. Vitamin E suppressed the DOX induced increase in LPO in the tumors of control mice, however, vitamin E was not sufficient to suppress a DOX induced increase in LPO in the tumors of FOC fed mice. The mean growth rate of tumors of FOC fed mice was significantly less than the mean growth rate of the tumors of control mice. Multiple regression analyses indicated that suppression of glutathione peroxidase (GPX) activity by FOC prior to DOX therapy was more important than increased LPO as an explanation of tumor growth suppression. Tumor induced cachexia was decreased in mice consuming FOC. It appears that the increased sensitivity to DOX was related to an FOC induced reduction in GPX activity. FOC reduced tumor induced cachexia.