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N-(6-氨基己基)-5-氯-1-萘磺酰胺(W-7)对小鼠皮肤中12-O-十四酰佛波醇-13-乙酸酯诱导的表皮鸟氨酸脱羧酶活性及肿瘤促进作用的抑制

Inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced epidermal ornithine decarboxylase activity and tumor promotion by N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) in mouse skin.

作者信息

Nakadate T, Yamamoto S, Aizu E, Kato R

出版信息

Pharmacology. 1986;32(3):167-75. doi: 10.1159/000138166.

DOI:10.1159/000138166
PMID:3083437
Abstract

N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) inhibited epidermal ornithine decarboxylase (ODC) induction caused either by 12-O-tetradecanoylphorbol-13-acetate (TPA) or teleocidin in CD-1 mice. Inhibitory effect of W-7 on TPA-caused ODC induction was also observed in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated skin and even after repetitive TPA treatment. TPA-induced skin tumor promotion was also suppressed by W-7. Meanwhile, W-7 showed only slight inhibitory effects on calcium-activated, phospholipid-dependent protein kinase (protein kinase C) activity of mouse epidermis stimulated either by Ca2+ or TPA in the presence of phosphatidylserine. Thus, it is unlikely that the anti-ODC-inducing and anti-tumor-promoting actions of W-7 are due to its inhibitory effect on protein kinase C. It may be possible that a calmodulin-mediating process is involved in the mechanism of epidermal ODC induction and tumor promotion caused by tumor promoters such as TPA and teleocidin.

摘要

N-(6-氨基己基)-5-氯-1-萘磺酰胺(W-7)可抑制12-O-十四烷酰佛波醇-13-乙酸酯(TPA)或杀鱼菌素在CD-1小鼠中引起的表皮鸟氨酸脱羧酶(ODC)诱导。在7,12-二甲基苯并[a]蒽(DMBA)引发的皮肤中,甚至在重复TPA处理后,也观察到W-7对TPA引起的ODC诱导的抑制作用。W-7还可抑制TPA诱导的皮肤肿瘤促进作用。同时,在磷脂酰丝氨酸存在的情况下,W-7对由Ca2+或TPA刺激的小鼠表皮的钙激活、磷脂依赖性蛋白激酶(蛋白激酶C)活性仅表现出轻微的抑制作用。因此,W-7的抗ODC诱导和抗肿瘤促进作用不太可能是由于其对蛋白激酶C的抑制作用。钙调蛋白介导的过程可能参与了由TPA和杀鱼菌素等肿瘤启动剂引起的表皮ODC诱导和肿瘤促进机制。

相似文献

1
Inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced epidermal ornithine decarboxylase activity and tumor promotion by N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) in mouse skin.N-(6-氨基己基)-5-氯-1-萘磺酰胺(W-7)对小鼠皮肤中12-O-十四酰佛波醇-13-乙酸酯诱导的表皮鸟氨酸脱羧酶活性及肿瘤促进作用的抑制
Pharmacology. 1986;32(3):167-75. doi: 10.1159/000138166.
2
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4
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6
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Gan. 1984 Mar;75(3):214-22.
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Cancer Res. 1986 Dec;46(12 Pt 1):6149-55.
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