促肿瘤佛波酯在体外刺激牛大脑皮质毛细血管内皮细胞生长。

Tumor-promoting phorbol esters stimulate bovine cerebral cortex capillary endothelial cell growth in vitro.

作者信息

Daviet I, Herbert J M, Maffrand J P

机构信息

Sanofi Recherche, Toulouse, France.

出版信息

Biochem Biophys Res Commun. 1989 Jan 31;158(2):584-9. doi: 10.1016/s0006-291x(89)80089-0.

DOI:10.1016/s0006-291x(89)80089-0

PMID:2917003

Abstract

The active tumor promoters, 12-O-tetradecanoyl phorbol 13-acetate (TPA) and phorbol 12, 13-dibutyrate (PDBu), which activate protein kinase C (PKC), were found to stimulate bovine brain cortex capillary endothelial cell (CEC) proliferation in a dose-dependent manner. 4 alpha-phorbol-12, 13-didecanoate (4 alpha-PDD), known to be inactive for PKC, was without effect in stimulating CEC proliferation. Furthermore, prolonged incubation with TPA led to a decrease in the number of [3H]-PDBu binding sites with a parallel loss of responses of the cells to TPA. Finally, staurosporine, a potent PKC inhibitor, showed a strong antiproliferative effect on CEC (IC50 = 1.3 nM). Therefore, this work suggests that PKC plays a fundamental role in CEC growth.

摘要

能够激活蛋白激酶C（PKC）的活性肿瘤启动子，即12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯（TPA）和佛波醇 - 12,13 - 二丁酸酯（PDBu），被发现能以剂量依赖的方式刺激牛脑皮质毛细血管内皮细胞（CEC）增殖。已知对PKC无活性的4α - 佛波醇 - 12,13 - 二癸酸酯（4α - PDD），在刺激CEC增殖方面没有作用。此外，用TPA长时间孵育导致[3H] - PDBu结合位点数量减少，同时细胞对TPA的反应也相应丧失。最后，强效PKC抑制剂星形孢菌素对CEC显示出强烈的抗增殖作用（IC50 = 1.3 nM）。因此，这项研究表明PKC在CEC生长中起重要作用。