Bernal-Ramos Gloria, Hernández-Gallegos Elisabeth, Vera Eunice, Chávez-López María De Guadalupe, Zúñiga-García Violeta, Sánchez-Pérez Yesennia, Garrido Efraín, Camacho Javier
Department of Genetics and Molecular Biology, Centro de Investigación y de Estudios Avanzados del I.P.N., Avenida Instituto Politécnico Nacional 2508, Mexico City 07360, Mexico.
Department of Pharmacology, Centro de Investigación y de Estudios Avanzados del I.P.N., Avenida Instituto Politécnico Nacional 2508, Mexico City 07360, Mexico.
Cell Mol Biol (Noisy-le-grand). 2017 Dec 17;63(12):11-13. doi: 10.14715/cmb/2017.63.12.4.
Prostate cancer (PC) is the main cause of cancer mortality in men worldwide. Therefore, novel treatments for PC are needed. Ether à-go-go-1 (Eag1) potassium channels display oncogenic properties, and have been suggested as early tumor markers and therapeutic targets for different cancers. These channels are overexpressed in many human tumors including PC. Astemizole targets several molecules involved in cancer including Eag1 channels, histamine receptors and ABC transporters. Here we studied Eag1 mRNA expression and protein levels in the non-tumorigenic and non-invasive human prostate RWPE-1 cell line, and in the tumorigenic and highly invasive human prostate WPE1-NB26 cell lines. The effect of astemizole on cell proliferation and apoptosis was also studied. The human prostate cell lines RWPE-1 and WPE1-NB26 were cultured following the provider´s instructions. Eag1 mRNA expression and protein levels were studied by real time RT-PCR and immunocytochemistry, respectively. Cell proliferation and apoptosis were studied by a fluorescence AlamarBlue® assay and flow cytometry, respectively. No difference in Eag1 mRNA expression was observed between the cell lines. However, high Eag1 protein levels were observed in the invasive WPE1-NB26 cells, in contrast to the weak protein expression in RWPE-1 cells. Accordingly, astemizole decreased cell proliferation at nanomolar concentrations only in the invasive WPE1-NB26 cells. Our results suggest that astemizole may have clinical relevance for prostate cancer treatment in patients with high Eag1 protein levels.
前列腺癌（PC）是全球男性癌症死亡的主要原因。因此，需要新的PC治疗方法。醚 - 去 - 去 - 1（Eag1）钾通道具有致癌特性，并已被建议作为不同癌症的早期肿瘤标志物和治疗靶点。这些通道在包括PC在内的许多人类肿瘤中过表达。阿司咪唑靶向多种参与癌症的分子，包括Eag1通道、组胺受体和ABC转运蛋白。在这里，我们研究了非致瘤性和非侵袭性人类前列腺RWPE - 1细胞系以及致瘤性和高侵袭性人类前列腺WPE1 - NB26细胞系中Eag1 mRNA表达和蛋白水平。还研究了阿司咪唑对细胞增殖和凋亡的影响。按照供应商的说明培养人类前列腺细胞系RWPE - 1和WPE1 - NB26。分别通过实时RT - PCR和免疫细胞化学研究Eag1 mRNA表达和蛋白水平。分别通过荧光AlamarBlue® 检测和流式细胞术研究细胞增殖和凋亡。在细胞系之间未观察到Eag1 mRNA表达的差异。然而，与RWPE - 1细胞中较弱的蛋白表达相比，在侵袭性WPE1 - NB26细胞中观察到高Eag1蛋白水平。因此，阿司咪唑仅在侵袭性WPE1 - NB26细胞中以纳摩尔浓度降低细胞增殖。我们的结果表明，阿司咪唑可能对Eag1蛋白水平高的前列腺癌患者的治疗具有临床意义。
