Voltage-gated sodium ion channels in prostate cancer: expression and activity

Abstract

Background: High levels of voltage-gated sodium channels (VGSCs) have been previously associated with the invasiveness of rat and human prostate cancer (Pca) cell lines.

Materials and methods: 4 normal prostate and 80 clinical Pca specimens on a tissue microarray slide were examined by immunohistochemistry using anti-sodium channel (III-IV linker region) antibody. The effects of a VGSC-opener and VGSC-blockers on the in vitro proliferation of 4 human Pca cell lines was examined.

Results: Fifty-five% (44 out of 80) Pca specimens showed higher VGSC levels compared to normal, with 14 (of 44) showing increased focal staining. VGSC-opener veratrine (1-50 microg/mL), increased growth of PC3, DU145, LNCaP and MDA-PCA-2B Pca cells. VGSC-blockers, flunarizine (IC50=2 microg/mL) and riluzole (IC50=10-30 microg/mL) caused dose-dependent growth-inhibition of all four cell lines. Western analysis of cell extracts showed VGSC-immunoreactivity in the 4 Pca cell lines.

Conclusion: Our results indicate increased expression of VGSCs in Pca and VGSC involvement in Pca growth.