Warburg effect in Gynecologic cancers
Warburg effect in Gynecologic cancers
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DOI：
10.1111/jog.13867
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发表时间：
2019-03-01
影响因子：
1.6
通讯作者：
Aoki, Daisuke
中科院分区：
文献类型：
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作者：
Kobayashi, Yusuke;Banno, Kouji;Aoki, Daisuke
哺乳动物细胞在有氧条件下通过氧化磷酸化产生能量。然而，在20世纪20年代，Otto Warburg报道了所谓的“Warburg效应”，即癌细胞不仅在无氧环境中而且在有氧环境中产生偏向于糖酵解而不是线粒体氧化磷酸化的ATP。葡萄糖在糖酵解中代谢后不进入线粒体而转化为乳酸。与氧化磷酸化相比，糖酵解的ATP产生速度更快，但效率很低，导致癌细胞消耗大量葡萄糖。葡萄糖代谢增加已成为癌细胞的生物标志物，并导致了氟脱氧葡萄糖正电子发射断层扫描的发展。迄今为止，瓦尔堡效应对于癌细胞来说在有效产生能量方面一直是一个低效的系统，但由于随着肿瘤大量生长，氧气的消耗可以被抑制，因此人们认为瓦尔堡效应在这种尽管缺乏血管但肿瘤仍会增大的情况下是有利的。此外，糖酵解引起的乳酸增加会导致组织微环境中的酸中毒，这被认为会损害周围的正常组织并有利于癌症的侵袭和转移。因此，瓦尔堡效应是癌症发展的关键机制之一，并将成为下一个有希望的目标。在这篇综述中，我们介绍了可以针对瓦尔堡效应的关键参与者，并概述了针对妇科癌症的瓦尔堡效应的治疗前景。
Mammalian cells produce energy by oxidative phosphorylation under aerobic conditions. However, in the 1920s, Otto Warburg reported the so-called "Warburg effect" in which cancer cells produce ATP that is biased toward glycolysis rather than mitochondrial oxidative phosphorylation not only in anaerobic environment but also in aerobic environment. Glucose is converted into lactate without going into mitochondria after being metabolized in glycolysis. Compared with oxidative phosphorylation, the glycolysis has a faster ATP production rate but it is very inefficient, resulting in cancer cells consuming a large amount of glucose. Increased glucose metabolism has become a biomarker for cancer cells and has led to the development of positron emission tomography with fluorodeoxyglucose. Till date, the Warburg effect has been an inefficient system for cancer cells with regard to efficient energy production, but since the consumption of oxygen can be suppressed as the tumor grows in mass, it is thought that the Warburg effect is advantageous in this situation wherein the tumor can increase despite the lack of vessels. In addition, an increased lactate by the glycolysis causes acidosis in the microenvironment of tissues, which is thought to damage the surrounding normal tissues and favor the invasion and metastasis of cancer. Thus, Warburg effect is one of the key mechanisms for cancer development and will be the next promising target. In this review, we introduce key players that can be targeted in the Warburg effect and outline the prospects of treatment, targeting the Warburg effect in gynecological cancer.