乳酸何去何从——运动抗肿瘤的作用及其特异性研究

    Where Lactate to Go?——Effects of Exercise on Anti-tumor and Its Specificities

    • 摘要: 乳酸是运动与肿瘤的共同代谢物。组织器官之间的乳酸穿梭是运动中骨骼肌快速合成ATP并维持工作能力的前提。运动与肿瘤发生风险负相关已成共识,但在乳酸代谢层面存在一定的矛盾,运动加快了乳酸在组织间周转,而“抗肿瘤”要求减少甚至切断乳酸穿梭。因此,首先讨论了4个与乳酸有关的机制冲突:1)运动乳酸生成对肿瘤微环境的利弊;2)运动激活乳酸脱氢酶对癌细胞生长的利弊;3)线粒体乳酸代谢是碳源循环利用还是加速肿瘤增长;4)乳酸诱导脂肪褐化是改善代谢还是加剧恶病质。为解决这些冲突,讨论了肌肉、肝脏、血液与癌细胞之间的乳酸交换机制,提出肌乳酸清除阈、肝乳酸转化阈、癌细胞乳酸阈、血乳酸阈等4个限制条件,进一步理解运动抗肿瘤的特异性。

       

      Abstract: Lactate is a common metabolite of exercise and cancer cell. Lactate shuttle is a prerequisite for skeletal muscles to rapidly synthesize ATP during exercise and maintain their contraction ability. The negative correlation between exercise and cancer risks has been well established, however, there is a conflict in the process of lactate metabolism, i.e., exercise promotes the turnover of lactate between muscle and other tissues, while“anti-tumor”requires reducing or even cutting off the lactate shuttle. Four conflicts related to lactate metabolism were firstly proposed as following: 1) The advantages or disadvantages of exercise-induced lactate to tumor microenvironment; 2) The advantages or disadvantages of exercise-activated lactate dehydrogenase to tumor growth; 3) Does mitochondrial lactate metabolism recycle muscle's carbon sources or promote tumor growth?4) Does lactate-induced fat browning improve metabolism or exacerbate cancer associated cachexia? To resolve these conflicts, the lactate exchanges between muscles,liver, blood and cancer cells were discussed in this review. Four hypotheses on lactate threshold were proposed to further understand the specificity of exercise in anti-tumor, and future directions and suggestions were also proposed for the personalized anti-tumor strategy.

       

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