Inhibition of CIP2A determines erlotinib-induced apoptosis in hepatocellular carcinoma

摘要: Abstract Erlotinib is a small-molecular inhibitor of epidermal growth factor receptor (EGFR). Here, we identify that cancerous protein phosphatase 2A (CIP2A) major determinant mediating erlotinib-induced apoptosis in hepatocellular carcinoma (HCC). showed differential effects on 4 human HCC cell lines. induced significant Hep3B and PLC5 lines; however, Huh-7 HA59 T lines resistance to at all tested doses. Down-regulation CIP2A, cellular (PP2A), mediated the apoptotic effect erlotinib HCC. inhibited CIP2A dose- time-dependent manner sensitive cells whereas no alterations were found resistant cells. Overexpression upregulated phospho-Akt protected from apoptosis. In addition, silencing by siRNA restored Moreover, adding okadaic acid, PP2A inhibitor, abolished cells; forskolin, agonist enhanced Combining Akt MK-2206 with sensitivity erlotinib. Furthermore, vivo xenograft data tumor but had tumor. downregulated activity tumors, not tumors. conclusion, inhibition determines may be useful as therapeutic biomarker for predicting clinical response treatment.