癌症干细胞（CSC）中激活的膜转运蛋白是肝细胞癌（HCC）新型癌症疗法的目标。本研究证实了 HCC CSC 中离子通道的表达谱。通过荧光激活细胞分选，从人 HCC 细胞系 HepG2 细胞中分离出高表达乙醛脱氢酶 1 家族成员 A1 (ALDH1A1) 的细胞，并将 CSCs根据肿瘤球的形成进行鉴定。使用微阵列分析研究 CSC 中的基因表达谱。在 HepG2 细胞中，CSC 中的 ALDH1A1 信使 RNA 水平高于非 CSC。此外，CSC表现出对顺铂的抗性并具有再分化的能力。 CSCs的微阵列分析结果显示，多个与离子通道相关的基因表达上调，例如钙电压门控通道辅助亚基γ4（CACNG4）。 CACNG4 抑制剂氨氯地平在 CSC 中的细胞毒性在较低浓度下高于非 CSC，并且显着减少肿瘤球的数量。该抑制剂也显着减少了高表达 ALDH1A1 的 HepG2 细胞中的细胞数量。CACNG4 在维持 CSC 中发挥作用，其抑制剂氨氯地平可能成为 HCC 的靶向治疗药物。版权所有 © 2023 国际抗癌研究所（乔治·J·德利纳西奥斯博士），保留所有权利。

The membrane transporters activated in cancer stem cells (CSCs) are the target of novel cancer therapies for hepatocellular carcinoma (HCC). The present investigation demonstrated the expression profiles of ion channels in CSCs of HCC.Cells that highly expressed aldehyde dehydrogenase 1 family member A1 (ALDH1A1) were separated from HepG2 cells, a human HCC cell line, by fluorescence-activated cell sorting, and CSCs were identified based on the formation of tumorspheres. Gene expression profiles in CSCs were investigated using microarray analysis.Among HepG2 cells, ALDH1A1 messenger RNA level was higher in CSCs than in non-CSCs. Furthermore, CSCs exhibited resistance to cisplatin and had the capacity to redifferentiate. The results of the microarray analysis of CSCs showed the up-regulated expression of several genes related to ion channels, such as calcium voltage-gated channel auxiliary subunit gamma 4 (CACNG4). The cytotoxicity of the CACNG4 inhibitor amlodipine was higher at lower concentrations in CSCs than in non-CSCs, and markedly decreased the number of tumorspheres. The cell population among HepG2 cells that highly expressed ALDH1A1 was also significantly reduced by this inhibitor.CACNG4 plays a role in maintaining CSCs, and its inhibitor, amlodipine, could potentially be a targeted therapeutic agent against HCC.Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.