title: Synergistic effect of Sorafenib and Sunitinib with Enzastaurin, a selective protein kinase C inhibitor in renal cell carcinoma cell lines.
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.
authors.affiliation: Clinical Division of Oncology, Department of Medicine I, Medical University Vienna, Waehringer Guertel 18-20, Vienna, Austria. ursula.vogl@meduniwien.ac.at
authors.forename: Ursula Maria
authors.initials: UM
authors.lastname: Vogl
authors.forename: Walter
authors.initials: W
authors.lastname: Berger
authors.forename: Michael
authors.initials: M
authors.lastname: Micksche
authors.forename: Christine
authors.initials: C
authors.lastname: Pirker
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Lamm
authors.forename: Oskar
authors.initials: O
authors.lastname: Pichelmeyer
authors.forename: Christoph C
authors.initials: CC
authors.lastname: Zielinski
authors.forename: Manuela
authors.initials: M
authors.lastname: Schmidinger
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001557:Benzenesulfonates / Q000494:pharmacology*; D002292:Carcinoma, Renal Cell; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D011725:Pyridines / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D019893:Ribosomal Protein S6 Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D000077157:Sorafenib; D000077210:Sunitinib
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D007211:Indoles; D010671:Phenylurea Compounds; D011725:Pyridines; D011758:Pyrroles; D009536:Niacinamide; D000077157:Sorafenib; D000071679:Glycogen Synthase Kinase 3 beta; D019893:Ribosomal Protein S6 Kinases; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D038362:Glycogen Synthase Kinase 3; C504878:enzastaurin; D000077210:Sunitinib