Nature:限制甲硫氨酸摄入或有助于抗癌治疗
创作:szx 审核:szx 2019年09月01日
  • 构建2种肿瘤小鼠模型:RAS驱动的化疗耐药性结直肠癌PDX模型、KRAS G12D突变及p53敲除共同驱动的放疗抗性自发性软组织肉瘤模型;
  • 在结直肠癌PDX模型中,限制甲硫氨酸摄入可改变甲硫氨酸及硫代谢,抑制肿瘤生长,并增强化疗(5-FU)的疗效;
  • 在自发性软组织肉瘤模型中,限制甲硫氨酸摄入可增强放疗的疗效;
  • 代谢组分析显示,限制甲硫氨酸摄入影响了肿瘤细胞的一碳代谢;
  • 限制甲硫氨酸摄入对人体代谢有着与在小鼠模型中相似的影响。
主编推荐语
szx
靶向代谢通路可影响癌症的治疗效果。Nature上发表的一项最新研究,在不同的肿瘤小鼠模型中发现,限制甲硫氨酸摄入可抑制肿瘤生长,并增强化疗或放疗的效果;而在人体试验中,限制甲硫氨酸摄入可引起与在小鼠模型中相似的代谢变化。
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Nature [IF:42.778]

Dietary methionine influences therapy in mouse cancer models and alters human metabolism

膳食甲硫氨酸影响小鼠肿瘤模型中的疗法并改变人体代谢

10.1038/s41586-019-1437-3

2019-07-31, Article

Abstract & Authors:展开

Abstract:收起
Nutrition exerts considerable effects on health, and dietary interventions are commonly used to treat diseases of metabolic aetiology. Although cancer has a substantial metabolic component1, the principles that define whether nutrition may be used to influence outcomes of cancer are unclear2. Nevertheless, it is established that targeting metabolic pathways with pharmacological agents or radiation can sometimes lead to controlled therapeutic outcomes. By contrast, whether specific dietary interventions can influence the metabolic pathways that are targeted in standard cancer therapies is not known. Here we show that dietary restriction of the essential amino acid methionine—the reduction of which has anti-ageing and anti-obesogenic properties—influences cancer outcome, through controlled and reproducible changes to one-carbon metabolism. This pathway metabolizes methionine and is the target of a variety of cancer interventions that involve chemotherapy and radiation. Methionine restriction produced therapeutic responses in two patient-derived xenograft models of chemotherapy-resistant RAS-driven colorectal cancer, and in a mouse model of autochthonous soft-tissue sarcoma driven by a G12D mutation in KRAS and knockout of p53 (KrasG12D/+;Trp53−/−) that is resistant to radiation. Metabolomics revealed that the therapeutic mechanisms operate via tumour-cell-autonomous effects on flux through one-carbon metabolism that affects redox and nucleotide metabolism—and thus interact with the antimetabolite or radiation intervention. In a controlled and tolerated feeding study in humans, methionine restriction resulted in effects on systemic metabolism that were similar to those obtained in mice. These findings provide evidence that a targeted dietary manipulation can specifically affect tumour-cell metabolism to mediate broad aspects of cancer outcome.

First Authors:
Xia Gao

Correspondence Authors:
Jason W Locasale

All Authors:
Xia Gao,Sydney M Sanderson,Ziwei Dai,Michael A Reid,Daniel E Cooper,Min Lu,John P Richie Jr,Amy Ciccarella,Ana Calcagnotto,Peter G Mikhael,Samantha J Mentch,Juan Liu,Gene Ables,David G Kirsch,David S Hsu,Sailendra N Nichenametla,Jason W Locasale

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BioArt微信公众号

Nature | 高霞博士等揭示蛋氨酸限制饮食可影响肿瘤的发生和治疗

2019-08-01

点评:来自BioArt的解读文章。

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食疗抗癌?今日《自然》为您支招

2019-08-01

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