美国宾夕法尼亚大学Maayan Levy和Christoph A. Thaiss共同合作，近期取得重要进展。他们研究发现β-羟基丁酸酯能抑制结直肠癌。该项研究成果2022年4月27日在线发表于《自然》杂志上。
在这里，研究人员确定了一种代谢物信号通路，为实现这一目标提供了可行的见解。他们在结直肠癌(CRC)的本土动物模型中进行了饮食筛选，发现生酮饮食表现出强烈的肿瘤抑制作用。酮体 β-羟基丁酸 (BHB) 重现了生酮饮食的这些特性，它减少了结肠隐窝细胞的增殖并有效地抑制了肠道肿瘤的生长。
研究人员发现BHB通过表面受体Hcar2起作用并诱导转录调节因子Hopx，从而改变基因表达并抑制细胞增殖。癌症类器官分析和CRC患者活检的单细胞RNA测序提供了证据，表明BHB水平升高和活性HOPX与人类肠上皮增殖减少有关。因此，本研究确定了BHB触发的调节肠道肿瘤发生的途径，并表明使用单一代谢物的口服或全身干预可以补充目前的CRC预防和治疗策略。
据介绍，结直肠癌(CRC)是最常见的癌症之一，迫切需要新的预防和治疗策略。
附：英文原文
Title: β-Hydroxybutyrate suppresses colorectal cancer
Author: Dmitrieva-Posocco, Oxana, Wong, Andrea C., Lundgren, Patrick, Golos, Aleksandra M., Descamps, Hlne C., Dohnalov, Lenka, Cramer, Zvi, Tian, Yuhua, Yueh, Brian, Eskiocak, Onur, Egervari, Gabor, Lan, Yemin, Liu, Jinping, Fan, Jiaxin, Kim, Jihee, Madhu, Bhoomi, Schneider, Kai Markus, Khoziainova, Svetlana, Andreeva, Natalia, Wang, Qiaohong, Li, Ning, Furth, Emma E., Bailis, Will, Kelsen, Judith R., Hamilton, Kathryn E., Kaestner, Klaus H., Berger, Shelley L., Epstein, Jonathan A., Jain, Rajan, Li, Mingyao, Beyaz, Semir, Lengner, Christopher J., Katona, Bryson W., Grivennikov, Sergei I., Thaiss, Christoph A., Levy, Maayan
Issue&Volume: 2022-04-27
Abstract: Colorectal cancer (CRC) is among the most frequent forms of cancer, and new strategies for its prevention and therapy are urgently needed1. Here we identify a metabolite signalling pathway that provides actionable insights towards this goal. We perform a dietary screen in autochthonous animal models of CRC and find that ketogenic diets exhibit a strong tumour-inhibitory effect. These properties of ketogenic diets are recapitulated by the ketone body β-hydroxybutyrate (BHB), which reduces the proliferation of colonic crypt cells and potently suppresses intestinal tumour growth. We find that BHB acts through the surface receptor Hcar2 and induces the transcriptional regulator Hopx, thereby altering gene expression and inhibiting cell proliferation. Cancer organoid assays and single-cell RNA sequencing of biopsies from patients with CRC provide evidence that elevated BHB levels and active HOPX are associated with reduced intestinal epithelial proliferation in humans. This study thus identifies a BHB-triggered pathway regulating intestinal tumorigenesis and indicates that oral or systemic interventions with a single metabolite may complement current prevention and treatment strategies for CRC.
DOI: 10.1038/s41586-022-04649-6
Source: https://www.nature.com/articles/s41586-022-04649-6
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
