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3%的膳食鱼油浓缩物可提高阿霉素对MDA-MB 231乳腺癌异种移植瘤的疗效。

Three percent dietary fish oil concentrate increased efficacy of doxorubicin against MDA-MB 231 breast cancer xenografts.

作者信息

Hardman W E, Avula C P, Fernandes G, Cameron I L

机构信息

Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229-3900, USA.

出版信息

Clin Cancer Res. 2001 Jul;7(7):2041-9.

Abstract

Omega 3 polyunsaturated fatty acids (the type of fat found in fish oil) have been used to kill or slow the growth of cancer cells in culture and in animal models and to increase the effectiveness of cancer chemotherapeutic drugs. An AIN-76 diet containing 5% corn oil (CO) was modified to contain 3% w/w fish oil concentrate (FOC) and 2% CO to test whether a clinically applicable amount of FOC is beneficial during doxorubicin (DOX) treatment of cancer xenografts in mice. Compared with the diet containing 5% CO, consumption of FOC increased omega 3 polyunsaturated fatty acids and lipid peroxidation in tumor and liver, significantly decreased the ratio of glutathione peroxidase activity to superoxide dismutase activity (a putative indicator of increased oxidative stress) in tumor but not in the liver, and significantly decreased the tumor-growth rate. The decreased glutathione peroxidase:superoxide dismutase ratio, indicating an altered redox state, in the tumor of FOC-fed mice was significantly correlated with decreased tumor-growth rate. Assay of the body weight change, blood cell counts, and number of micronuclei in peripheral erythrocytes indicated that the toxicity of DOX to the host mouse was not increased in mice fed FOC. Thus, a small amount of FOC increased the effectiveness of DOX but did not increase the toxicity of DOX to the host mouse. These positive results justify clinical testing of FOC in conjunction with cancer chemotherapy.

摘要

欧米伽3多不饱和脂肪酸(鱼油中所含的脂肪类型)已被用于在细胞培养和动物模型中杀死癌细胞或减缓其生长,并提高癌症化疗药物的疗效。将含有5%玉米油(CO)的AIN-76饮食进行改良,使其含有3%重量/重量的鱼油浓缩物(FOC)和2%的CO,以测试临床上适用量的FOC在小鼠癌症异种移植模型接受阿霉素(DOX)治疗期间是否有益。与含有5%CO的饮食相比,食用FOC可增加肿瘤和肝脏中欧米伽3多不饱和脂肪酸及脂质过氧化作用,显著降低肿瘤中谷胱甘肽过氧化物酶活性与超氧化物歧化酶活性的比值(氧化应激增加的一个假定指标),但对肝脏无此影响,且显著降低肿瘤生长速率。FOC喂养小鼠的肿瘤中谷胱甘肽过氧化物酶:超氧化物歧化酶比值降低,表明氧化还原状态改变,这与肿瘤生长速率降低显著相关。对体重变化、血细胞计数和外周红细胞微核数量的检测表明,FOC喂养的小鼠中DOX对宿主小鼠的毒性并未增加。因此,少量FOC可提高DOX的疗效,但不会增加DOX对宿主小鼠的毒性。这些积极结果证明了FOC与癌症化疗联合进行临床试验的合理性。

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