Blocking the Nav1.5 channel using eicosapentaenoic acid reduces migration and proliferation of ovarian cancer cells
Blocking the Nav1.5 channel using eicosapentaenoic acid reduces migration and proliferation of ovarian cancer cells
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使用二十碳五烯酸阻断 Nav1.5 通道可减少卵巢癌细胞的迁移和增殖
DOI：
10.3892/ijo.2018.4437
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发表时间：
2018-08-01
影响因子：
5.2
通讯作者：
Hong, Liang
中科院分区：
文献类型：
--
作者：
Liu, Junxiu;Liu, Dawei;Hong, Liang
据报道，电压门控Nav1.5钠通道的活性参与细胞增殖、癌症侵袭和基因表达。此外，二十碳五烯酸（EPA）最近被认为可以抑制卵巢癌细胞的生长和抑制肿瘤转移。本研究旨在探讨EPA、Nav1.5钠通道与卵巢癌细胞的关系。应用膜片钳技术和RNA干扰技术，在上皮性卵巢癌细胞上记录钠电流，证实Nav1.5通道携带钠电流。EPA能剂量依赖性地抑制钠电流，使钠电流的稳态失活曲线向超极化方向移动，降低钠窗口电流。此外，EPA以剂量依赖性方式诱导灭活曲线的移动。通过EPA或通过Nav1.5敲低抑制钠通道，减弱卵巢癌细胞迁移和增殖。据我们所知，本研究首次在卵巢癌细胞中进行钠电流记录，并揭示EPA可能抑制Nav1.5介导的卵巢癌细胞迁移和生长。这些发现不仅为卵巢癌提供了一个潜在的预后生物标志物，而且为卵巢癌患者开发新的药物治疗提供了一种策略。
Activity of the voltage-gated Nav1.5 sodium channel has been reported to be involved in cell proliferation, cancer invasion and gene expression. In addition, eicosapentaenoic acid (EPA) has recently been suggested to inhibit ovarian cancer cell growth and suppress tumor metastasis. The present study aimed to explore the association between EPA, the Nav1.5 sodium channel and ovarian cancer cells. Using patch-clamp technique and RNA interference approaches, sodium currents were recorded in epithelial ovarian cancer cells, and it was confirmed that the Nav1.5 channel carried the sodium currents. Furthermore, EPA effectively inhibited sodium currents in a dose-dependent manner, shifted the steady-state inactivation curve of sodium currents to the hyperpolarizing direction and reduced sodium window currents. In addition, EPA induced a shift in the inactivation curve in a dose-dependent manner. Inhibition of the sodium channel, either by EPA or by Nav1.5 knockdown, attenuated ovarian cancer cell migration and proliferation. To the best of our knowledge, the present study is the first to conduct sodium current recording in ovarian cancer cells, and revealed that EPA may inhibit Nav1.5-mediated ovarian cancer cell migration and growth. These findings not only present a potential prognostic biomarker for ovarian cancer, but also provide a strategy towards the development of novel pharmacological treatments for patients with ovarian cancer.