Abstract: Objective To investigate the expressions of extracellular signal-regulated kinase (ERK) and the BH3-only subgroup
of Bcl-2 related proteins (Bim) in multidrug-resistant hepatocellular carcinoma (HCC) cells and their association with drug
resistance in the cells. Methods The multdrug-resistant HepG-2 cell line was established by treatment with gradually
increasing doses of ADM. CCK-8 assay was used to determine the drug sensitivity of the cells, and the expressions of MRP-1,
P-gp, ERK1, ERK2, ERK5, and Bim were detected with Western blot. Bim mRNA expression level was measured using
quantitative real-time PCR. Results The drug resistance indices to ADM, 5-FU and CDDP was 6.8, 4.10, and 4.5 in HepG-2/
ADM cells, respectively. The drug-resistantcells showed marked up-regulation of MRP-1, P-gp, ERK1, ERK2 and ERK5 with
down-regulated phosphorylated ERK2 protein expression but no significant changes in phosphorylated ERK1 protein
expression to result in a decreased ratio of P-ERK1/2 and P-ERK1/2. Bim mRNA and protein expressions were both decreased
in HepG-2/ADM cells. Conclusion ERK and Bim are related to multidrug resistance in HepG-2/ADM cells.