Institute of Physiology II, University of Münster, Münster, Germany.
Rev Physiol Biochem Pharmacol. 2021;181:57-79. doi: 10.1007/112_2020_29.
Ion channels are a major class of membrane proteins that play central roles in signaling within and among cells, as well as in the coupling of extracellular events with cellular responses. Dysregulated ion channel activity plays a causative role in many diseases including cancer. Here, we will review their role in lung cancer. Lung cancer is one of the most frequently diagnosed cancers, and it causes the highest number of deaths of all cancer types. The overall 5-year survival rate of lung cancer patients is only 19% and decreases to 5% when patients are diagnosed with stage IV. Thus, new therapeutical strategies are urgently needed. The important contribution of ion channels to the progression of various types of cancer has been firmly established so that ion channel-based therapeutic concepts are currently developed. Thus far, the knowledge on ion channel function in lung cancer is still relatively limited. However, the published studies clearly show the impact of ion channel inhibitors on a number of cellular mechanisms underlying lung cancer cell aggressiveness such as proliferation, migration, invasion, cell cycle progression, or adhesion. Additionally, in vivo experiments reveal that ion channel inhibitors diminish tumor growth in mice. Furthermore, some studies give evidence that ion channel inhibitors can have an influence on the resistance or sensitivity of lung cancer cells to common chemotherapeutics such as paclitaxel or cisplatin.
离子通道是一类主要的膜蛋白,它们在细胞内和细胞间的信号转导中起着核心作用,也在细胞外事件与细胞反应的偶联中发挥作用。离子通道活性失调在许多疾病中起着致病作用,包括癌症。在这里,我们将回顾它们在肺癌中的作用。肺癌是最常见的癌症之一,也是所有癌症类型中导致死亡人数最多的癌症。肺癌患者的总体 5 年生存率仅为 19%,而当患者被诊断为 IV 期时,生存率下降到 5%。因此,迫切需要新的治疗策略。离子通道对各种类型癌症进展的重要贡献已经得到了确凿的证实,因此基于离子通道的治疗概念正在被开发。迄今为止,关于离子通道在肺癌中的功能的知识仍然相对有限。然而,已发表的研究清楚地表明,离子通道抑制剂对肺癌细胞侵袭性的许多细胞机制(如增殖、迁移、侵袭、细胞周期进展或黏附)有影响。此外,体内实验表明,离子通道抑制剂可减少小鼠的肿瘤生长。此外,一些研究表明,离子通道抑制剂可以影响肺癌细胞对紫杉醇或顺铂等常用化疗药物的耐药性或敏感性。