恶性肿瘤线粒体丙酮酸代谢障碍研究进展

Mitochondrial pyruvate metabolism disorder in malignant tumors

目的肿瘤细胞的生物学特征都与线粒体异常的能量代谢作用存在千丝万缕的联系,恢复线粒体内丙酮酸正常代谢途径可达到控制或清除肿瘤的效果。本研究主要探讨丙酮酸在肿瘤细胞线粒体中的代谢情况及其机制的研究,也讨论了以肿瘤细胞的氧化代谢为靶标的新的癌症治疗方法。方法检索PubMed数据库检索系统,以"肿瘤细胞、丙酮酸、线粒体"为关键词,检索2000-01-01-2017-12-31的相关文献。纳入标准:与肿瘤细胞线粒体丙酮酸转运的文献;与肿瘤细胞线粒体内丙酮酸氧化代谢异常相关的文献;与肿瘤细胞线粒体内丙酮酸羧化异常相关的文献。剔除标准:重复性文献;发表时间较久远的文献;机制阐述不明确的文献。根据纳入标准及剔除标准符合分析的文献53篇。结果肿瘤细胞中普遍存在线粒体丙酮酸载体的减少或功能丧失。大多数肿瘤细胞中存在丙酮酸脱氢酶复合体的活性降低导致丙酮酸在线粒体内氧化障碍。丙酮酸羧化酶介导的葡萄糖依赖的回补反应可能是一些肿瘤细胞维持增殖和生长所必须的。丙酮酸代谢是细胞能量代谢的关键,针对癌细胞异常丙酮酸代谢的药物开发应该是可以预见成效的。结论恶性肿瘤的线粒体丙酮酸代谢障碍可以成为很好的靶向药物作用靶点,但面临诸多挑战,还需进一步探索与研究。

OBJECTIVE The biological characteristics of tumor cells are all linked to the abnormal energy metabolism of mitochondria, and restoration of the normal metabolic pathway of pyruvate in mitochondria can achieve the effect of controlling or eliminating cancer.In this study, the metabolism and mechanism of pyruvic acid in the mitochondria of tumor cells were studied,and a new method of cancer treatment which was the target of the oxidation metabolism of tumor cells, was discussed.METHODS Publications from 2000 to 2017 on the study of research advances of targeted agents were searched by the key words of "tumor cells,pyruvate and mitochondna" from publication databases such as PubMed.Totally 53 articles were collected in accordance with the inclusion criterion.Inclusion criteria: literatures on mitochondrial pyruvate transport in tumor cells;literatures related to abnormal oxidative pyruvate metabolism in mitochondria of tumor cells;literatures related to abnormal carboxylation of pyruvate in mitochondria of tumor cells.Exclusion criteria: repetitive literature;a relatively long time publication;mechanism is not clear.RESULTS The decrease of mitochondrial pyruvate carrier or loss of function is common in tumor cells.The decrease in activity of pyruvate dehydrogenase complex in most of the tumor cells leads to the oxidative disorder of pyruvate in the mitochondria.The Glucose dependent response mediated by pyruvate carboxylase may be necessary for the proliferation and growth of some tumor cells.Pgruvate metabolism is the key to cell energy metabolism.The development of drugs for abnormal pgruvate metabolism in cancer cells should be predictable.CONCLUSIONS Mitochondrial pyruvate metabolism disorder of malignant tumors can be a good target for drug targeting,but it facing many challenges and needs further exploration and research.