No transcriptional evidence for active Nav channels in two classes of cancer cell

IF 3.3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Channels Pub Date : 2019-01-01 DOI:10.1080/19336950.2019.1644858

Supanida Hompoonsup, D. Chambers, P. Doherty, Gareth Williams

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引用次数: 1

Abstract

ABSTRACT Voltage-gated sodium channel (Nav) expression in non-excitable cells has raised questions regarding their non-canonical roles. Interestingly, a growing body of evidence also points towards the prevalence of aberrant Nav expression in malignant tumors, potentially opening a new therapeutic window. In this study, the transcriptional consequences of channel inhibition were investigated in non-small cell lung carcinoma H460 and neuroblastoma SH-SYSY cell lines, that both express Nav1.7. Channel activity was blocked by the application of both selective, ProTx-II, and non-selective, tetrodotoxin, inhibitors. Global gene expression profiling did not point to any statistically significant inhibition-associated perturbation of the transcriptome. A small subset of genes that showed relatively consistent changes across multiple treatments were further assayed in the context of a multiplex bead expression array which failed to recapitulate the changes seen in the global array. We conclude that there is no robust transcriptional signature associated with the inhibition of two sodium channel expressing cancer cell lines and consequently sodium channel inhibition will not lend itself to therapeutic approaches such as transcription-based drug repurposing.

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在两类癌细胞中没有活性Nav通道的转录证据

电压门控钠通道(Nav)在不可兴奋细胞中的表达引起了人们对其非规范作用的质疑。有趣的是，越来越多的证据也指向了恶性肿瘤中Nav异常表达的普遍存在，这可能会打开一个新的治疗窗口。本研究在表达Nav1.7的非小细胞肺癌H460和神经母细胞瘤SH-SYSY细胞系中研究了通道抑制的转录后果。通道活性被选择性的ProTx-II和非选择性的河豚毒素抑制剂阻断。全球基因表达谱没有指出任何统计学上显著的抑制相关的转录组扰动。在多重头表达阵列的背景下，进一步分析了在多种处理中表现出相对一致变化的一小部分基因，该基因未能概括全局阵列中所见的变化。我们得出的结论是，没有强大的转录特征与抑制两种表达钠通道的癌细胞系相关，因此钠通道抑制将不适合用于治疗方法，如基于转录的药物再利用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Channels 生物-生化与分子生物学

CiteScore

5.90

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Channels is an open access journal for all aspects of ion channel research. The journal publishes high quality papers that shed new light on ion channel and ion transporter/exchanger function, structure, biophysics, pharmacology, and regulation in health and disease. Channels welcomes interdisciplinary approaches that address ion channel physiology in areas such as neuroscience, cardiovascular sciences, cancer research, endocrinology, and gastroenterology. Our aim is to foster communication among the ion channel and transporter communities and facilitate the advancement of the field.