Zhao Yanyan, Wang Jiaying, Liu Xuehui
Department of Respiratory Medicine, Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
Braz J Med Biol Res. 2021 Oct 18;54(12):e10867. doi: 10.1590/1414-431X2021e10867. eCollection 2021.
Lung cancer is one of the most common cancers worldwide. TRPV4 belongs to the 'transient receptor potential' (TRP) superfamily. It has been identified to profoundly affect a variety of physiological processes, including nociception, heat sensation, and inflammation. Unlike other TRP superfamily channels, its roles in cancers are unknown. Here, we elucidated the effects of TRPV4 and molecular mechanisms in human lung cancer cells. The levels of TRPV4 were detected in human lung cancer tissues and the paired paracarcinoma tissues by real-time PCR and western blotting analysis. The proliferation of human lung cancer cells was determined by MTT assay. Cell apoptosis was determined by FACS assay. The results demonstrated that low levels of TRPV4 were detected in clinical lung carcinoma specimens. Over-expression of TRPV4 induced cell death and inhibited cell proliferation and migration in A549 cells and H460 cells. Moreover, over-expression of TRPV4 enhanced the activation of p38 MAPK signal pathway. Inhibition of p38 MAPK abolished the effects of TRPV4 on cell proliferation, apoptosis, and migration in A549 cells. Collectively, our findings indicated that TRPV4 induced apoptosis via p38 MAPK in human lung cancer cells and suggested that TRPV4 was a potential target for therapy of human lung cancers.
肺癌是全球最常见的癌症之一。TRPV4属于“瞬时受体电位”（TRP）超家族。已确定它会深刻影响多种生理过程，包括痛觉、热感觉和炎症。与其他TRP超家族通道不同，其在癌症中的作用尚不清楚。在此，我们阐明了TRPV4在人肺癌细胞中的作用及其分子机制。通过实时PCR和蛋白质印迹分析检测人肺癌组织及配对的癌旁组织中TRPV4的水平。通过MTT法测定人肺癌细胞的增殖情况。通过流式细胞术检测细胞凋亡。结果表明，在临床肺癌标本中检测到低水平的TRPV4。TRPV4的过表达诱导细胞死亡，并抑制A549细胞和H460细胞的增殖和迁移。此外，TRPV4的过表达增强了p38 MAPK信号通路的激活。抑制p38 MAPK消除了TRPV4对A549细胞增殖、凋亡和迁移的影响。总体而言，我们的研究结果表明，TRPV4通过p38 MAPK诱导人肺癌细胞凋亡，并提示TRPV4是人类肺癌治疗的潜在靶点。
