Abstract

The purpose of this study was to investigate the effects of chloride (Cl⁻) channels on the adhesive and invasive potentials of human ovarian cancer cell line A2780. By using the adhesion and Transwell invasion assays, we showed that 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid (200 μmol/L), a nonselective Cl⁻ channel blocker, significantly inhibits cancer cell adhesion and invasion. 5-Nitro-2-(3-phenylpropylamino)-benzoate (200 μmol/L), niflumic acid (100 μmol/L), and tamoxifen (30 μmol/L) had similar inhibitory effects. Regulatory volume decrease is markedly suppressed by 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid, 5-nitro-2-(3-phenylpropylamino)-benzoate, niflumic acid, and tamoxifen. Moreover, intracellular calcium concentration ([Ca²⁺]_i) measurements indicated that a Cl⁻ channel-mediated increase in [Ca²⁺]_i is also one of the mechanisms of cancer cell adhesion and invasion. Our results strongly suggest that Cl⁻ channels may regulate ovarian cancer cell adhesion and invasion, probably through inducing a regulatory volume decrease and mediating a [Ca²⁺]_i increase.