College of Pharmacy, Umm Al-Qura University, Al-Abidiyya, 21955 Makkah, Saudi Arabia.
Child Health, Obstetrics and Gynaecology, School of Medicine, University of Nottingham, Maternity Unit, City Hospital Nottingham, Nottingham NG7 1PB, UK.
Semin Cancer Biol. 2017 Apr;43:42-48. doi: 10.1016/j.semcancer.2017.01.002. Epub 2017 Jan 8.
The role of the Warburg effect in cancer remains to be elucidated with a resurgence in research efforts over the past decade. Why a cancer cell would prefer to use energy inefficient glycolysis, leading to an alteration of pH both inside and outside of the cell, remains to be uncovered. The development of MDR represents a major challenge in the treatment of cancer and it is explained, so far, by the over expression of drug transporters such as the well-known and archetypal P-glycoprotein (Pgp). However, controversies exist regarding the function of Pgp in multi-drug resistance. We suggest here that Pgp-mediated MDR relies fundamentally on pH alterations mediated by the Warburg effect. Furthermore, we propose that the use of proton pump and/or transporters inhibitors (PPIs/PTIs) in cancer are key to controlling both MDR, i.e. sensitize tumors to antineoplastic agents, and drug-related adverse effects.
沃伯格效应在癌症中的作用仍有待阐明，过去十年的研究工作再次兴起。为什么癌细胞宁愿选择能量效率低下的糖酵解，导致细胞内外 pH 值发生变化，这仍然是一个未解之谜。多药耐药的发展是癌症治疗的一个主要挑战，迄今为止，它被解释为药物转运蛋白的过度表达，如著名的典型 P-糖蛋白（Pgp）。然而，关于 Pgp 在多药耐药中的作用存在争议。我们在这里提出，Pgp 介导的多药耐药依赖于沃伯格效应介导的 pH 变化。此外，我们还提出，在癌症中使用质子泵和/或转运体抑制剂（PPIs/PTIs）是控制多药耐药的关键，即使肿瘤对抗肿瘤药物敏感，并减少与药物相关的不良反应。
