Lidocaine Inhibits Rat Prostate Cancer Cell Invasiveness and Voltage-Gated Sodium Channel Expression in Plasma Membrane.

IF 2.3 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Journal of Membrane Biology Pub Date : 2024-04-01 Epub Date: 2024-01-02 DOI:10.1007/s00232-023-00302-z
Nahit Rizaner, Scott P Fraser, Ilknur Bugan Gul, Esma Purut, Mustafa B A Djamgoz, Seyhan Altun
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引用次数: 0

Abstract

There is increasing evidence, mostly from breast cancer, that use of local anaesthetics during surgery can inhibit disease recurrence by suppressing the motility of the cancer cells dependent on inherent voltage-gated sodium channels (VGSCs). Here, the possibility that lidocaine could affect cellular behaviours associated with metastasis was tested using the Dunning cell model of rat prostate cancer. Mostly, the strongly metastatic (VGSC-expressing) Mat-LyLu cells were used under both normoxic and hypoxic conditions. The weakly metastatic AT-2 cells served for comparison in some experiments. Lidocaine (1-500 μM) had no effect on cell viability or growth but suppressed Matrigel invasion dose dependently in both normoxia and hypoxia. Used as a control, tetrodotoxin produced similar effects. Exposure to hypoxia increased Nav1.7 mRNA expression but VGSCα protein level in plasma membrane was reduced. Lidocaine under both normoxia and hypoxia had no effect on Nav1.7 mRNA expression. VGSCα protein expression was suppressed by lidocaine under normoxia but no effect was seen in hypoxia. It is concluded that lidocaine can suppress prostate cancer invasiveness without effecting cellular growth or viability. Extended to the clinic, the results would suggest that use of lidocaine, and possibly other local anaesthetics, during surgery can suppress any tendency for post-operative progression of prostate cancer.

Abstract Image

利多卡因抑制大鼠前列腺癌细胞的侵袭性和浆膜中电压门控钠通道的表达
越来越多的证据(主要来自乳腺癌)表明,在手术过程中使用局部麻醉剂可以通过抑制依赖于固有电压门控钠通道(VGSCs)的癌细胞的运动来抑制疾病的复发。在此,我们使用大鼠前列腺癌的邓宁细胞模型对利多卡因影响与转移相关的细胞行为的可能性进行了测试。在常氧和缺氧条件下,主要使用了强转移性(表达 VGSC)的 Mat-LyLu 细胞。在某些实验中,转移性较弱的 AT-2 细胞被用作对比。利多卡因(1-500 μM)对细胞活力或生长没有影响,但在常氧和缺氧条件下都能抑制 Matrigel 的侵袭。作为对照,河豚毒素也产生了类似的效果。缺氧会增加 Nav1.7 mRNA 的表达,但质膜上的 VGSCα 蛋白水平会降低。在常氧和缺氧条件下,利多卡因对 Nav1.7 mRNA 的表达没有影响。利多卡因在常氧条件下抑制了 VGSCα 蛋白的表达,但在缺氧条件下则没有影响。结论是利多卡因可抑制前列腺癌的侵袭性,而不会影响细胞的生长或存活率。将这些结果推广到临床中,将表明在手术过程中使用利多卡因(也可能是其他局部麻醉剂)可以抑制前列腺癌术后进展的任何趋势。
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来源期刊
Journal of Membrane Biology
Journal of Membrane Biology 生物-生化与分子生物学
CiteScore
4.80
自引率
4.20%
发文量
63
审稿时长
6-12 weeks
期刊介绍: The Journal of Membrane Biology is dedicated to publishing high-quality science related to membrane biology, biochemistry and biophysics. In particular, we welcome work that uses modern experimental or computational methods including but not limited to those with microscopy, diffraction, NMR, computer simulations, or biochemistry aimed at membrane associated or membrane embedded proteins or model membrane systems. These methods might be applied to study topics like membrane protein structure and function, membrane mediated or controlled signaling mechanisms, cell-cell communication via gap junctions, the behavior of proteins and lipids based on monolayer or bilayer systems, or genetic and regulatory mechanisms controlling membrane function. Research articles, short communications and reviews are all welcome. We also encourage authors to consider publishing ''negative'' results where experiments or simulations were well performed, but resulted in unusual or unexpected outcomes without obvious explanations. While we welcome connections to clinical studies, submissions that are primarily clinical in nature or that fail to make connections to the basic science issues of membrane structure, chemistry and function, are not appropriate for the journal. In a similar way, studies that are primarily descriptive and narratives of assays in a clinical or population study are best published in other journals. If you are not certain, it is entirely appropriate to write to us to inquire if your study is a good fit for the journal.
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