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Cancer Lett ; 277(2): 218-26, 2009 May 18.
Article in English | MEDLINE | ID: mdl-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.


Subject(s)
Antineoplastic Agents/pharmacology , Benzenesulfonates/pharmacology , Cell Proliferation/drug effects , Indoles/pharmacology , Pyridines/pharmacology , Pyrroles/pharmacology , Carcinoma, Renal Cell , Cell Cycle/drug effects , Cell Line, Tumor , Drug Resistance, Neoplasm , Drug Synergism , Glycogen Synthase Kinase 3/antagonists & inhibitors , Glycogen Synthase Kinase 3/metabolism , Glycogen Synthase Kinase 3 beta , Humans , Niacinamide/analogs & derivatives , Phenylurea Compounds , Protein Kinase C , Protein Kinase C beta , Ribosomal Protein S6 Kinases/antagonists & inhibitors , Ribosomal Protein S6 Kinases/metabolism , Signal Transduction , Sorafenib , Sunitinib
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