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人类肺瘤中的乳酸代谢

Brandon Faubert¹, Kevin Y Li¹, Ling Cai²

¹Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.

|October 7, 2017

概括

瘤,包括非小细胞肺癌 (NSCLC),可以利用乳酸作为能量来源. 这项研究表明,乳酸是NSCLC三酸循环的主要燃料.

科学领域:

癌症学
癌症新陈代谢
生物化学

背景情况:

癌细胞代谢葡萄糖,分泌乳酸.
乳酸在活体瘤的能量代谢中的作用尚不清楚.
之前的研究表明,人类非小细胞肺癌 (NSCLC) 在三碳酸 (TCA) 循环中利用葡萄糖.

研究的目的:

调查乳酸是否作为NSCLC中TCA循环的碳来源.
在人体NSCLC中确定乳酸利用的程度.
为了比较乳酸与葡萄糖对瘤代谢的贡献.

主要方法:

给人类NSCLC患者注入13C乳酸盐.
对TCA循环代谢物标记的分析
在小鼠瘤模型中,单碳酸盐转运体-1 (MCT1) 的遗传删除.
在体内代谢流量分析,比较乳酸和葡萄糖.

主要成果:

乳酸被确定为人类NSCLC中TCA循环的重要碳来源.
乳酸利用在具有高18-氧葡萄糖吸收和攻击性行为的瘤中更为明显.
在小鼠中通过MCT1删除证实了瘤细胞自主吸收乳酸.
在体内,乳酸对TCA循环的贡献超过了葡萄糖.

结论:

人类NSCLC和其他瘤可以在体内利用乳酸作为燃料来源.
乳酸在癌细胞的代谢重编程中起着至关重要的作用.
针对乳酸代谢是一种潜在的NSCLC治疗策略.

关键词:

癌症代谢葡萄糖溶解乳酸盐肺部癌症代谢流量分析单碳酸盐的运输三碳酸循环华堡效应

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