Background: Nav1.5, an isoform of voltage-gated sodium channel alpha subunits, has been found to be over-expressed in cancer cells and linked to disease progression. Nav1.5-third extracellular region antibody (E3Ab) specifically targets the E3 of Nav1.5 and can lead to a subtype-specific inhibition of Nav1.5. We were interested in the therapeutic potential of E3Ab in cancer.
Methods: The Nav1.5 expression in Caov-3 cells was assessed by immunocytochemistry. The effect of E3Ab on tumor growth in vivo was evaluated by using a nude mouse xenograft model derived from Caov-3 cells. In vitro, SiHa, MDA-MB-231, and Caov-3 cells were treated with E3Ab and cell migration, invasion, and proliferation were evaluated by transwell assays and EdU. Metal matrix protease-9 (MMP-9) expression was analyzed by Western blot.
Results: We found that Caov-3 cells highly expressed Nav1.5 and its binding with E3Ab was confirmed. In vivo, the growth of Caov-3 xenografts was significantly inhibited by E3Ab or lidocaine compared to control. The treatment with E3Ab and lidocaine significantly reduced the mitotic activity in tumor. E3Ab, as well as lidocaine, could inhibit the migration and invasion ability of cancer cells in vitro.
Conclusions: These findings suggest that E3Ab is a potential new therapeutic antibody for treatment of cancers expressing Nav1.5.
Keywords: Ion channel; Nav1.5; cancer; invasion; migration.
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