Abstract
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 strategytowards the development of novel pharmacological treatments for patients with ovarian cancer.
Highlights
Ovarian cancer is one of the most common types of cancer among women worldwide, resulting in >14,000 cases of mortality each year [1]
The present study hypothesized that eicosapentaenoic acid (EPA) may affect the Nav1.5 channel in ovarian cancer cells; the results indicated that treatment with 15 μM EPA blocked ~60% sodium currents in SKOV3 cancer cells (Fig. 3A, B and E), and this inhibition could be completely reversed following EPA washout (Fig. 3C and D)
The migration of Nav1.5 siRNA-transfected cells was not further reduced by 200 μM EPA, indicating that the impaired invasion of these cells was due to the absence of Nav1.5 activities (Fig. 8B). These results suggested that the Nav1.5 channel may have a critical role in ovarian cancer migration, and the effects of EPA on cell migration were due to the blockade of Nav1.5 sodium channels
Summary
Ovarian cancer is one of the most common types of cancer among women worldwide, resulting in >14,000 cases of mortality each year [1]. Epithelial ovarian cancer is the most common type of ovarian cancer, which has the highest mortality rate of all gynecological malignancies. This high mortality rate is largely due to the lack of an effective biomarker; in addition, it is difficult to diagnose patients at the early stage of the disease and most patients are diagnosed at advanced stages [2,3,4]. The Nav1.5 channel protein is a member of the voltagegated sodium channel family [5]. It is the predominant sodium channel in cardiomyocytes and permeates sodium currents to initiate the action potential duration in the heart [6]. Growing evidence has suggested that the Nav1.5 channel is implicated in ovarian cancer development [11,12], suggesting that small molecule-induced inhibition of this channel may lead to a novel pharmacological treatment
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