在癌细胞中，碳酸酐酶12被认为是一个致癌和酸性微环境因子。为了验证组胺信号通路在抗癌信号中的作用，我们确定了CA12和其相关碳酸氢盐转运体的功能。在本研究中，组胺刺激介导了CA12在肺癌细胞中的错位。组胺受体激活介导的CA12内吞和pH可以通过CaMKII抑制来恢复。CA12相关的AE2表达增强，而组胺刺激导致了NBCn1表达和其活性的降低。组胺受体激活介导的酸化是通过内源性的CA12和NBCn1以及增强的AE2表达引起的碳酸氢盐流出增加而诱导的。通过巴吡溴铵抑制蛋白质运输恢复CA12和AE2的定位，并减弱细胞酸中毒。因此，我们验证了组胺刺激诱导了一个酸性环境，在肺癌细胞中展示了CA12及其相关碳酸氢盐转运体的转运，并且其调控的pH改变可能参与了组胺信号介导的抗癌过程。

Carbonic anhydrase 12 is considered an oncogenic and acidic microenvironmental factor in cancer cells. To verify the role of histamine signalling as an anti-cancer signal, we determined the roles of CA12 and its associated bicarbonate transporters. In this study, histamine stimulation mediated mislocalization of CA12 in lung cancer cells. Histamine receptor activation-mediated CA12 endocytosis and pH were restored by CaMKII inhibition. CA12-associated AE2 expression was enhanced, whereas NBCn1 expression and its activity were reduced by histamine stimulation. Histamine receptor activation-mediated acidification was induced by internalised CA12 and NBCn1 and, at the same time by increased bicarbonate efflux through enhanced AE2 expression. Inhibition of protein trafficking by bafilomycin restored CA12 and AE2 localisation and diminished cellular acidosis. Thus, we verified that histamine stimulation induced an acidic scenario, which revealed trafficking of CA12 and its associated bicarbonate transporters in lung cancer cells and its dysregulated pH modulation may be involved in the histamine signalling-mediated anti-cancer process.