a Department of Pharmacology , Faculty of Pharmacy, AL-Neelain University , Khartoum , Sudan.
J Enzyme Inhib Med Chem. 2016 Dec;31(6):859-66. doi: 10.3109/14756366.2016.1140753. Epub 2016 Feb 10.
Cancer cells reprogram their metabolic machineries to enter into permanent glycolytic pathways. The full reason for such reprogramming takes place is unclear. However, this metabolic switch is not made in vain for the lactate that is generated and exported outside cells is reused by other cells. This results in the generation of a pH gradient between the low extracellular pH that is acidic (pHe) and the higher cytosolic alkaline or near neutral pH (pHi) environments that are tightly regulated by the overexpression of several pumps and ion channels (e.g. NHE-1, MCT-1, V-ATPase, CA9, and CA12). The generation of this unique pH gradient serves as a determining factor in defining "tumor fitness". Tumor fitness is the capacity of the tumor to invade and metastasize due to its ability to reduce the efficiency of the immune system and confer resistance to chemotherapy. In this article, we highlight the importance of tumor microenvironment in mediating the failure of chemotherapeutic agents.
癌细胞重新编程其代谢机制，进入永久性糖酵解途径。这种重新编程发生的全部原因尚不清楚。然而，这种代谢转换并非徒劳无功，因为细胞外产生的乳酸被其他细胞重新利用。这导致细胞外低 pH 值（酸性 pHe）和细胞内高胞质碱性或近中性 pH 值（pHi）之间产生 pH 梯度，这种梯度受到几种泵和离子通道（例如 NHE-1、MCT-1、V-ATPase、CA9 和 CA12）的过度表达的严格调节。这种独特的 pH 梯度的产生是定义“肿瘤适应性”的决定因素。肿瘤适应性是指肿瘤由于能够降低免疫系统的效率并赋予对化疗的抗性而侵袭和转移的能力。在本文中，我们强调了肿瘤微环境在介导化疗药物失效中的重要性。
