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.
Li
Min
M
Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong, PR China.
Wang
Qing
Q
Lin
Wei
W
Wang
Bo
B
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006801:Humans; D009361:Neoplasm Invasiveness; D009544:Niflumic Acid / Q000494:pharmacology; D009579:Nitrobenzoates / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D013629:Tamoxifen / Q000494:pharmacology
D018118:Chloride Channels; D009579:Nitrobenzoates; D013629:Tamoxifen; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D009544:Niflumic Acid; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D005905:Glyburide; D002118:Calcium