Lee Y S, Sayeed M M, Wurster R D
Department of Neurological Surgery, Loyola University Medical Center, Maywood, Ill. 60153.
Pharmacology. 1994 Aug;49(2):69-74. doi: 10.1159/000139218.
The effect of cromakalim, a K+ channel opener, on the growth of human brain tumor cells was investigated. Cromakalim inhibited the growth of SK-N-MC human neuroblastoma and U-373 MG human astrocytoma cell lines in a dose-dependent manner. This effect of cromakalim was significantly blocked by the co-treatment with sulfonylureas (glibenclamide or tolbutamide) which are known as specific blockers for ATP-sensitive K+ channels. In addition, cromakalim significantly inhibited agonist-induced intracellular Ca2+ mobilization in the astrocytoma cells. This inhibition induced by cromakalim was also reversed by pretreatment with glibenclamide. These results suggest that the antitumor activity of cromakalim may be due to the activation of ATP-sensitive K+ channels leading to the inhibition of the intracellular Ca2+ signalling mechanism.
研究了钾离子通道开放剂克罗卡林对人脑肿瘤细胞生长的影响。克罗卡林以剂量依赖性方式抑制SK - N - MC人神经母细胞瘤和U - 373 MG人星形细胞瘤细胞系的生长。与作为ATP敏感性钾通道特异性阻滞剂的磺脲类药物（格列本脲或甲苯磺丁脲）联合处理可显著阻断克罗卡林的这种作用。此外，克罗卡林显著抑制星形细胞瘤细胞中激动剂诱导的细胞内钙离子动员。格列本脲预处理也可逆转克罗卡林所诱导的这种抑制作用。这些结果表明，克罗卡林的抗肿瘤活性可能是由于ATP敏感性钾通道的激活导致细胞内钙离子信号传导机制受到抑制。
