电压门控钠通道亚型Nav1.5在乳腺癌细胞中的表达及与细胞体外转移的关系

NaV1.5 Potentiates in vitro Metastasis Behaviour of MDA-MB-231 Human Breast Cancer Cells

目的观察电压门控钠通道(voltage-gated sodiumchannels,VGSCs)亚型在乳腺癌细胞中的表达及其与细胞体外转移的关系。方法通过RT-PCR,Western blot,MTT及Transwell小室迁移和侵袭实验,检测乳腺癌细胞MDA-MB-231和MCF-7中VGSCs的表达及VGSCs特异性阻断剂河豚毒素(TTX)对细胞的毒性、迁移和侵袭特性的影响。结果在MDA-MB-231细胞和MCF-7细胞中同时存在NaV1.1,NaV1.4和NaV1.8的高表达;而在MDA-MB-231细胞中发现NaV1.3和NaV1.5、NaV1.6的表达量较MCF-7细胞中明显升高,尤其是NaV1.5的表达具有功能性意义。体外应用1μmol/L和30μmol/L TTX处理细胞后,与对照组相比,MDA-MB-231细胞的体外侵袭性分别下降了(12.50±0.19)%和(53.58±1.03)%,而MCF-7细胞的体外侵袭性却没有发生明显变化。结论乳腺癌细胞MDA-MB-231中存在高表达的NaV1.5,TTX阻断VGSCs后显著抑制其体外侵袭力。

Objective To explore the effect of voltage-gated sodium channels（VGSCs） on metabasis behavior of human breast cancer cell lines MDA-MB-231 and MCF-7. Methods RT-PCR,Western blot, MTT and Transwell assays were respectively used to detect the expression of VGSCs and the effect of specific VGSCs inhibitor TTX on cell toxicity,and migration and invasion of MDA-MB-231 and MCF-7 cells. Results Nav1. 1, Navl. 4 and Navl. 8 were over-expressed in MDA-MB-231 and MCF-7 ceils. The expression levels of Nav1. 3 ,Navl. 5 and Navl. 6 mRNA in MDA-MB-231 cells were higher than in MCF-7 cells, especially Navl. 5 had the functional protein expression. After treatment with 1 and 30 μmol/L TTX in vitro, the invasive capacities of MDA-MB-231 cells were decreased （ 12.50±0.19） % and （ 53.58 ± 1.03） % respectively, while those of MCF-7 cells had no obvious changes. Conclusion NaV1.5 was over-expressed in MDA-MB-231 cells,and TTX could reduce their invasive behaviors by inhibiting the activity of VGSCs.