Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, Guizhou Province, China.
Digestive Disease Institute of Guizhou Province, Zunyi, Guizhou Province, China.
Cell Oncol (Dordr). 2021 Aug;44(4):739-749. doi: 10.1007/s13402-021-00604-1. Epub 2021 Apr 15.
Gastric cancer (GC) is one of the most common malignant cancers in the world and has only few treatment options and, concomitantly, a poor prognosis. It is generally accepted now that the tumor microenvironment, particularly that under hypoxia, plays an important role in cancer development. Hypoxia can regulate the energy metabolism and malignancy of tumor cells by inducing or altering various important factors, such as oxidative stress, reactive oxygen species (ROS), hypoxia-inducible factors (HIFs), autophagy and acidosis. In addition, altered expression and/or dysfunction of ion channels/transporters (ICTs) have been encountered in a variety of human tumors, including GC, and to play an important role in the processes of tumor cell proliferation, migration, invasion and apoptosis. Increasing evidence indicates that ICTs are at least partly involved in interactions between cancer cells and their hypoxic microenvironment. Here, we provide an overview of the different ICTs that regulate or are regulated by hypoxia in GC.
Hypoxia is one of the major obstacles to cancer therapy. Regulating cellular responses and factors under hypoxia can inhibit GC. Similarly, altering the expression or activity of ICTs, such as the application of ion channel inhibitors, can slow down the growth and/or migration of GC cells. Since targeting the hypoxic microenvironment and/or ICTs may be a promising strategy for the treatment of GC, more attention should be paid to the interplay between ICTs and the development and progression of GC in such a microenvironment.
胃癌（GC）是世界上最常见的恶性肿瘤之一，治疗选择有限，预后较差。现在普遍认为肿瘤微环境，特别是缺氧环境，在癌症发展中起着重要作用。缺氧可以通过诱导或改变各种重要因素，如氧化应激、活性氧（ROS）、缺氧诱导因子（HIFs）、自噬和酸中毒，来调节肿瘤细胞的能量代谢和恶性程度。此外，在包括 GC 在内的多种人类肿瘤中，离子通道/转运体（ICTs）的表达和/或功能异常已经遇到，并在肿瘤细胞增殖、迁移、侵袭和凋亡过程中发挥重要作用。越来越多的证据表明，ICTs 至少部分参与了癌细胞与其缺氧微环境之间的相互作用。在这里，我们概述了调节 GC 缺氧的不同 ICTs。
缺氧是癌症治疗的主要障碍之一。调节缺氧下的细胞反应和因素可以抑制 GC。同样，改变 ICTs 的表达或活性，如应用离子通道抑制剂，可以减缓 GC 细胞的生长和/或迁移。由于靶向缺氧微环境和/或 ICTs 可能是治疗 GC 的一种有前途的策略，因此应该更加关注 ICTs 与 GC 在这种微环境中的发展和进展之间的相互作用。
