Objective      To establish sorafenib-indeuced drug resistant hepatoma cell lines and investigate their biological characteristics.        Methods      CCK8 assay was used for drug sensitivity of hepatocellular carcinoma cell lines PLC/PRF/5 and Huh7 to sorafenib. By using intermittent induction in vitro and the obtained IC

50

value as a screening concentration

we screened and established drug resistant cell lines. Expression of drug resistant genes

GST-π

LRP

MDR1

MRP and Topo Ⅱ

were examined by real time-PC

R. Western blot analysis was applied to examine the phosphorylation level of extracellular regulated protein kinases 1/2 (ERK1/2).       Results      Sorafenib-resistant PLC/PRF/5 and Huh7 cells had a longer survival rate compared with corresponding control cells (P0.05). MDR1 was the only one from the 5 resistance genes who had significantly increased expression (P0.05). Furthermore

sorafenib was found to induce the phosphorylation of ERK1/2.       Conclusion      Sorafenib resistant hepatoma cell lines PLC/PRF/5 and Huh7 are successfully established. The underlying mechanism may be associated with sorafenib-induced ERK1/2 activation that leads to high expression of drug resistant gene MDR1.