Background

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.

Conclusions and perspectives

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.

中文翻译：

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缺氧微环境中离子通​​道/转运蛋白的改变和功能障碍导致胃癌的发生和进展

背景

胃癌（GC）是世界上最常见的恶性肿瘤之一，治疗选择很少，预后较差。目前人们普遍认为肿瘤微环境，特别是缺氧条件下的肿瘤微环境，在癌症的发生发展中发挥着重要作用。缺氧可以通过诱导或改变氧化应激、活性氧（ROS）、缺氧诱导因子（HIF）、自噬和酸中毒等多种重要因素来调节肿瘤细胞的能量代谢和恶性程度。此外，离子通道/转运蛋白（ICT）的表达改变和/或功能障碍在包括GC在内的多种人类肿瘤中都存在，并且在肿瘤细胞增殖、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，ICT 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 GC 中调节缺氧或受缺氧调节的不同 ICT。

结论和观点

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子可以抑制GC。同样，改变 ICT 的表达或活性，例如应用离子通道抑制剂，可以减缓 GC 细胞的生长和/或迁移。由于针对低氧微环境和/或 ICT 可能是治疗 GC 的一种有前景的策略，因此应更多地关注 ICT 与此类微环境中 GC 的发生和进展之间的相互作用。