PROTEIN-KINASE-C AND ADENYLATE-CYCLASE AS TARGETS FOR GROWTH-INHIBITION OF HUMAN GASTRIC-CANCER CELLS

被引:13
作者
PIONTEK, M
HENGELS, KJ
PORSCHEN, R
STROHMEYER, G
机构
[1] Department of Gastroenterology, Heinrich-Heine-University, Düsseldorf, D-40001
关键词
PROTEIN KINASE-C; TPA; STAUROSPORINE; ADENYLATE CYCLASE; FORSKOLIN; BT2CAMP; GASTRIC CARCINOMA;
D O I
10.1007/BF01195338
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
In the human gastric adenocarcinoma cell line AGS the effects of the protein-kinase-C-activating phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA), the protein kinase C inhibitor staurosporine, the adenylate-cyclase activating agent forskolin, and the permeable dibutyryl-adenosine 3',5'-monophosphate (Bt2cAMP) on the proliferation were assessed. Cell counting followed 5 days of incubation. Prolonged activation of protein kinase C by TPA, inhibition of protein kinase C by staurosporine, activation of adenylate cyclase by forskolin or a direct increase of the intracellular cAMP level all result in a dose-dependent growth inhibition of AGS gastric tumour cells. Half-maximal inhibition was achieved at 100 pM for TPA, 1 nM for staurosporine, 20 muM for forskolin, and 600 muM for Bt2cAMP. It is concluded that protein kinase C and adenylate cyclase play a fundamental role in the growth of AGS gastric cancer cells. Interference with these enzymes involved in the signal transduction of growth regulation in tumour cells may represent a target in the development of new antiproliferative principles.
引用
收藏
页码:697 / 699
页数:3
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