Suppression of T-type Ca2+ channels inhibited human laryngeal squamous cell carcinoma cell proliferation running title: roles of T-type Ca2+ channels in LSCC cell proliferation.

Abstract

Despite the tight correlation between T-type Ca2+ channels and a great variety of tumors, the roles of alpha1G subunit of T-type Ca2+ channels in laryngeal squamous cell carcinoma (LSCC) have not yet been investigated. In the present study, we examined the expression of alpha1G subunit of T-type Ca2+ channel in human LSCC tissues and cell lines. One human laryngeal squamous cell carcinoma cell line, Hep-2, was also examined for T-type channels using voltage-clamp recordings. Cell proliferation assays were performed in the presence or absence of T-type channel blocker mibefradil and alpha1G subunit sepcific siRNA. The cell cycle was determined by flow cytometry. Our results indicated that the a1G subunit of T-type Ca2+ channel is highly expressed in human laryngeal squamous cell carcinoma tissues and cell lines. alpha1G siRNA significantly down-regulated the protein expression of the alpha1G subunit. Both alpha1G siRNA and mibefradil inhibited Hep-2 cell proliferation and arrested cell cycle progression. Together, these findings suggest a functional role of T-type channels in certain laryngeal carcinomas, and that inhibition of T-type channels reduces cell proliferation via cell cycle arrest, suggesting that the alpha1G subunit of T-type Ca2+ channel may be used as a therapeutic target for treating LSCC.