The Effects of a Novel MEK Inhibitor PD184161 on MEK-ERK Signaling and Growth in Human Liver Cancer

The MEK-ERK growth signaling pathway is important in human hepatocellular carcinoma (HCC). To evaluate the targeting of this pathway in HCC, we characterized a novel, orally-active MEK inhibitor, PD184161, using human HCC cells (HepG2, Hep3B, PLC, and SKHep) and in vivo human tumor xenografts. PD184161 inhibited MEK activity (IC50 = 10-100 nM) in a time- and concentrationdependent manner more effectively than PD098059 or U0126. PD184161...