Role of Lactate Dehydrogenase in Tumor Metabolism and Progress of LDH-targeted Drugs
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摘要:
能量代谢异常是肿瘤的特征性病理变化之一。有研究表明，肿瘤细胞即使在有氧情况下，也选择糖酵解方式并在乳酸脱氢酶A（LDHA）帮助下生成乳酸和少量ATP（即著名的瓦伯格效应）。细胞内过多的乳酸将在细胞膜上单羧酸转运蛋白4（MCT4）作用下转运至细胞外，并导致肿瘤细胞微环境pH值降低，同时肿瘤细胞微环境中的乳酸又可以被MCT1转运至邻近相对富氧区域的肿瘤细胞，并在LDHB的作用下，重新转变成丙酮酸用于氧化磷酸化。LDH在肿瘤能量代谢重编程中的重要作用，使其成为抗肿瘤治疗的新靶点。本文回顾了LDH与肿瘤细胞能量代谢之间的关系，并重点讨论了LDH在肿瘤发生发展中的作用，以及以LDH为靶点抗肿瘤药物研究的进展。
Abstract:Abnormal energy metabolism is one of the main hallmarks of cancer. Studies have shown that tumor cells, even in the presence of oxygen, favored glycolysis to produce lactic acid and a small amount of ATP with the help of LDHA in the cytosol (the famous Warburg effect). The excessive lactate is then exported to the extracellular space in the presence of monocarboxylate transporters (MCTs, primarily MCT4), resulting in the decrease of microenvironment pH value. On the other hand, the lactate in the tumor microenvironment will be re-absorbed in adjacent oxygenated tumor cells through the transporter MCT1 and finally transformed into pyruvate for oxidative phosphorylation under the effect of LDHB. The important effects of LDH in tumor energy metabolism reprogramming make it a new target for tumor therapy. In this review, we discussed briefly on the relation between LDH and energy metabolism of tumor cells, especially its effects on the process of tumor as well as the progress of LDH-targeted anti-tumor drugs.
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Key words:
- Lactate /
- Lactic dehydrogenase /
- Warburg effect /
- Pyruvate metabolism
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Competing interests: The authors declare that they have no competing interests.作者贡献丘金梅：论文构思、撰写与修改龚娟、谢青池：参与论文撰写及文献收集与整理谢志忠：论文构思、写作指导及审阅
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