The voltage-gated sodium channel Nav1.7 associated with endometrial cancer

Background: Endometrial cancer is the most common gynecologic malignancy in women in the developed countries. Despite recent progress in functional characterization of voltage-gated sodium channel (Na-v) in multiple cancers, very little was known about the expression of Na-v in human endometrial cancer. The present study sought to determine the role of Na-v and molecular nature of this channel in the endometrial cancer. Methods: PCR approach was introduced to determine expression level of Na-v subunits in endometrial cancer specimens. Pharmacological agents were used to investigate Na-v function in endometrial cancer cells. Flow cytometry were used to test cancer apoptosis, and invasion assays were applied to test tumor metastasis. Results: Transcriptional levels of the all Na-v alpha and beta subunits were determined by real time-PCR in endometrial cancer with pair tissues of carcinoma and adjacent nonneoplastic tissue, Na(v)1.7 was the most highly expressed Na-v subtype in endometrial cancer tissues. Na(v)1.7 level was closely associated with tumor size, local lymph node metastasis, and 5-year and 10-year survival ratio. Inhibition of this channel by Na(v)1.7 blocker PF-05089771, promoted cancer apoptosis and attenuated cancer cell invasion. Conclusion: These results establish a relationship between voltage-gated sodium channel protein and endometrial cancer, and suggest that Na(v)1.7 is a potential prognostic biomarker and could serve as a novel therapeutic target for endometrial cancer.