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

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.