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补充β-羟基-β-甲基丁酸可在体外降低肿瘤生长和肿瘤细胞增殖,并通过改变核因子-κB的表达来预防Walker 256荷瘤大鼠的恶病质。

Beta-hydroxy-beta-methylbutyrate supplementation reduces tumor growth and tumor cell proliferation ex vivo and prevents cachexia in Walker 256 tumor-bearing rats by modifying nuclear factor-kappaB expression.

作者信息

Nunes Everson Araújo, Kuczera Diogo, Brito Gleisson Alisson Pereira, Bonatto Sandro J R, Yamazaki Ricardo Key, Tanhoffer Ricardo Antonio, Mund Rogéria Campus, Kryczyk Marcelo, Fernandes Luiz Claudio

机构信息

Department of Physiology, Biological Science Building, Federal University of Paraná, 81531-980 Curitiba-PR, Brazil.

出版信息

Nutr Res. 2008 Jul;28(7):487-93. doi: 10.1016/j.nutres.2008.04.006.

DOI:10.1016/j.nutres.2008.04.006
PMID:19083450
Abstract

Cancer cachexia syndrome contributes to wasting and weight loss leading to inefficacy of anticancer therapy. In this study, the anticatabolic agent beta-hydroxy-beta-methylbutyrate (HMB) was supplemented to adult Walker 256 tumor-bearing rats during 8 weeks aiming to determine if tumor burden could be reduced. Male Wistar rats were randomly assigned to nontumor and tumor-bearing groups and fed regular chow or regular chow plus HMB supplemented (76 mg/kg body weight). Beta-hydroxy-beta-methylbutyrate supplementation induced a lower tumor weight and tumor cell proliferation ex vivo, totally prevented glycemia reduction, as well as blunted the increase in the serum lactate concentrations and also preserved glycogen stores in tumor-bearing rats. Reduction in tumor cell proliferation ex vivo was accompanied by increased nuclear factor-kappaB inhibitor-alpha content by more than 100%. In contrast, nuclear factor-kappaB p65 subunit content was suppressed by 17% with HMB supplementation. In conclusion, HMB supplementation, at a similar dose used in humans to increase muscle mass, caused antitumor and anticachectic effects, with tumor-cell nuclear factor-kappaB pathway participation, which might be a potential nutritional strategy in cancer therapy.

摘要

癌症恶病质综合征会导致消瘦和体重减轻,进而使抗癌治疗失效。在本研究中,在8周时间内给成年携带Walker 256肿瘤的大鼠补充抗分解代谢剂β-羟基-β-甲基丁酸酯(HMB),旨在确定肿瘤负荷是否能够降低。将雄性Wistar大鼠随机分为非肿瘤组和肿瘤携带组,并分别喂食普通饲料或添加HMB(76毫克/千克体重)的普通饲料。补充β-羟基-β-甲基丁酸酯可使肿瘤重量降低,体外肿瘤细胞增殖减少,完全防止血糖降低,还能抑制血清乳酸浓度的升高,并保留肿瘤携带大鼠的糖原储备。体外肿瘤细胞增殖的减少伴随着核因子-κB抑制因子-α含量增加超过100%。相反,补充HMB后核因子-κB p65亚基含量被抑制了17%。总之,以在人类中用于增加肌肉量的类似剂量补充HMB,可产生抗肿瘤和抗恶病质作用,涉及肿瘤细胞核因子-κB途径,这可能是癌症治疗中的一种潜在营养策略。

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Beta-hydroxy-beta-methylbutyrate supplementation reduces tumor growth and tumor cell proliferation ex vivo and prevents cachexia in Walker 256 tumor-bearing rats by modifying nuclear factor-kappaB expression.补充β-羟基-β-甲基丁酸可在体外降低肿瘤生长和肿瘤细胞增殖,并通过改变核因子-κB的表达来预防Walker 256荷瘤大鼠的恶病质。
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