Dietary restriction reduces angiogenesis and growth in an orthotopic mouse brain tumour model.
Dietary restriction reduces angiogenesis and growth in an orthotopic mouse brain tumour model.
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DOI：
10.1038/sj.bjc.6600298
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发表时间：
2002-05-20
影响因子：
8.8
通讯作者：
Seyfried, T N
中科院分区：
文献类型：
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作者：
Mukherjee, P;El-Abbadi, M M;Kasperzyk, J L;Ranes, M K;Seyfried, T N
饮食和生活方式对肿瘤的发病率、患病率和自然病程产生重大影响。长期以来，适度的饮食限制一直被认为是一种自然疗法，可以改善健康，促进长寿，并减少许多肿瘤类型的发病率和生长。饮食限制与禁食或饥饿不同，它减少食物和热量的总摄入量，而不引起营养缺乏。以前没有研究评估恶性脑癌对饮食限制的反应。我们发现，30-40%的适度饮食限制显著抑制了CT-2A同基因恶性小鼠星形细胞瘤的脑内生长，抑制率几乎达到80%。自由采食对照组（n=9）和饮食限制实验组（n=10）的总膳食摄入量分别约为20和13千卡/天。饮食限制喂养的小鼠的总体健康状况和活力优于随意喂养的小鼠。肿瘤微血管密度（因子VIII免疫染色）是在饮食限制的小鼠比在自由采食的小鼠的两倍，而肿瘤凋亡指数（TUNEL法）是在饮食限制的小鼠比在自由采食的小鼠的三倍。CT-2A肿瘤细胞诱导的血管分布在体内Matrigel plug测定中，在饮食限制小鼠中也比在自由采食小鼠中少。这些发现表明，饮食限制抑制CT-2A的生长，减少血管生成和增强细胞凋亡。饮食限制可以通过对肿瘤细胞和肿瘤相关宿主细胞的多重影响将肿瘤微环境从促血管生成状态转变为抗血管生成状态。我们的数据表明，适度的饮食限制可能是一种有效的抗血管生成治疗复发性恶性脑癌。英国癌症杂志（2002）86，1615-1621。DOI：10.1038/sj/bjc/6600298 www.bjcancer.com © 2002英国癌症研究中心
Diet and lifestyle produce major effects on tumour incidence, prevalence, and natural history. Moderate dietary restriction has long been recognised as a natural therapy that improves health, promotes longevity, and reduces both the incidence and growth of many tumour types. Dietary restriction differs from fasting or starvation by reducing total food and caloric intake without causing nutritional deficiencies. No prior studies have evaluated the responsiveness of malignant brain cancer to dietary restriction. We found that a moderate dietary restriction of 30–40% significantly inhibited the intracerebral growth of the CT-2A syngeneic malignant mouse astrocytoma by almost 80%. The total dietary intake for the ad libitum control group (n=9) and the dietary restriction experimental group (n=10) was about 20 and 13 Kcal day−1, respectively. Overall health and vitality was better in the dietary restriction-fed mice than in the ad libitum-fed mice. Tumour microvessel density (Factor VIII immunostaining) was two-fold less in the dietary restriction mice than in the ad libitum mice, whereas the tumour apoptotic index (TUNEL assay) was three-fold greater in the dietary restriction mice than in the ad libitum mice. CT-2A tumour cell-induced vascularity was also less in the dietary restriction mice than in the ad libitum mice in the in vivo Matrigel plug assay. These findings indicate that dietary restriction inhibited CT-2A growth by reducing angiogenesis and by enhancing apoptosis. Dietary restriction may shift the tumour microenvironment from a proangiogenic to an antiangiogenic state through multiple effects on the tumour cells and the tumour-associated host cells. Our data suggest that moderate dietary restriction may be an effective antiangiogenic therapy for recurrent malignant brain cancers. British Journal of Cancer (2002) 86, 1615–1621. DOI: 10.1038/sj/bjc/6600298 www.bjcancer.com © 2002 Cancer Research UK