索拉非尼和舒尼替尼与恩扎妥林（一种选择性蛋白激酶C抑制剂）在肾癌细胞系中的协同作用。

Synergistic effect of Sorafenib and Sunitinib with Enzastaurin, a selective protein kinase C inhibitor in renal cell carcinoma cell lines.

作者信息

Vogl Ursula Maria, Berger Walter, Micksche Michael, Pirker Christine, Lamm Wolfgang, Pichelmeyer Oskar, Zielinski Christoph C, Schmidinger Manuela

机构信息

Clinical Division of Oncology, Department of Medicine I, Medical University Vienna, Waehringer Guertel 18-20, Vienna, Austria.

出版信息

Cancer Lett. 2009 May 18;277(2):218-26. doi: 10.1016/j.canlet.2008.12.013. Epub 2009 Jan 25.

DOI:10.1016/j.canlet.2008.12.013

PMID:19171421

Abstract

Enzastaurin (LY317615.HCl) is an oral selective PKC-beta inhibitor with antiproliferative efficacy in various tumor models. This study was designed to investigate whether combination therapy with Enzastaurin and other targeted agents including Sorafenib and Sunitinib enhanced anti-tumor efficacy in renal cell carcinoma cell lines. Enzastaurin alone presented not active in renal cell carcinoma cell lines. Both Sorafenib and Sunitinib with Enzastaurin at concentrations feasible in vivo showed a synergistic reduction of viable RCC cells by inhibiting cell growth through inhibition of phospho-S6-kinase and GSK3-beta. The combination of Enzastaurin with Sorafenib and Sunitinib seems highly encouraging and warrants further investigation in vivo.

摘要

恩扎妥林（LY317615.HCl）是一种口服选择性蛋白激酶C-β抑制剂，在多种肿瘤模型中具有抗增殖功效。本研究旨在调查恩扎妥林与包括索拉非尼和舒尼替尼在内的其他靶向药物联合治疗是否能增强肾癌细胞系的抗肿瘤疗效。单独使用恩扎妥林在肾癌细胞系中无活性。索拉非尼和舒尼替尼与恩扎妥林在体内可行的浓度下联合使用，通过抑制磷酸化S6激酶和糖原合成酶激酶3-β来抑制细胞生长，从而协同降低存活的肾癌细胞数量。恩扎妥林与索拉非尼和舒尼替尼联合使用似乎很有前景，值得进一步进行体内研究。