Regulation of ovarian cancer cell adhesion and invasion by chloride channels.

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 micromol/L), a nonselective Cl channel blocker, significantly inhibits cancer cell adhesion and invasion. 5-Nitro-2-(3-phenylpropylamino)-benzoate (200 micromol/L), niflumic acid (100 micromol/L), and tamoxifen (30 micromol/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 C- 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.