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环肌酸抑制具有肌酸激酶的肿瘤细胞的刺激运动性。

Cyclocreatine inhibits stimulated motility in tumor cells possessing creatine kinase.

作者信息

Mulvaney P T, Stracke M L, Nam S W, Woodhouse E, O'Keefe M, Clair T, Liotta L A, Khaddurah-Daouk R, Schiffmann E

机构信息

Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

出版信息

Int J Cancer. 1998 Sep 25;78(1):46-52. doi: 10.1002/(sici)1097-0215(19980925)78:1<46::aid-ijc9>3.0.co;2-x.

Abstract

Cyclocreatine (1-carboxymethyl-2-iminoimidazolidine), an analog of creatine and a substrate for creatine kinase (EC 2.7.3.2), inhibits the stimulated motility of tumor cells which possess creatine kinase. A2058-055 human melanoma cells, transfected with a creatine kinase gene, showed an 80-90% reduction in chemotactic response to type IV collagen when incubated overnight in the presence of 10 mM cyclocreatine (p < 0.0001 for n = 8 experiments). This inhibitory effect of cyclocreatine can be partially reversed by addition of creatine to the overnight cell treatment. Non-transfected cells, with very low levels of creatine kinase, were not significantly inhibited. Further experiments utilizing type IV collagen as attractant demonstrated that cyclocreatine inhibited the chemokinetic (91%) and the haptotactic (73%) responses and the in vitro invasion of A2058-055 cells through Matrigel-coated membranes (88%). In addition, motility stimulation of A2058-055 cells by either autotaxin or fibronectin was markedly inhibited by cyclocreatine. DU-145 prostatic tumor cells, which express endogenous creatine kinase, also have a reduced motility response to either autotaxin or epidermal growth factor induced motility in the presence of cyclocreatine.

摘要

环肌酸(1-羧甲基-2-亚氨基咪唑烷)是肌酸的类似物,也是肌酸激酶(EC 2.7.3.2)的底物,它能抑制具有肌酸激酶的肿瘤细胞的刺激运动性。转染了肌酸激酶基因的A2058-055人黑色素瘤细胞,在10 mM环肌酸存在下孵育过夜后,对IV型胶原的趋化反应降低了80-90%(8次实验,p < 0.0001)。在过夜细胞处理中加入肌酸可部分逆转环肌酸的这种抑制作用。肌酸激酶水平极低的未转染细胞未受到显著抑制。利用IV型胶原作为趋化剂的进一步实验表明,环肌酸抑制了A2058-055细胞的化学动力学反应(91%)、触觉反应(73%)以及通过基质胶包被膜的体外侵袭(88%)。此外,环肌酸显著抑制自分泌运动因子或纤连蛋白对A2058-055细胞运动性的刺激。表达内源性肌酸激酶的DU-145前列腺肿瘤细胞,在环肌酸存在下,对自分泌运动因子或表皮生长因子诱导的运动性反应也降低。

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