AIM: To establish a multidrug resistant (MDR) cell sub- line from the human hepatocarcinoma cell line (HepG2) in nude mice. METHODS: HepG2 cell cultures were incubated with increasing concentrations of adriamycin (ADM) to develop an ADM-resistant cell subline (HepG2/ADM) with cross- resistance to other chemotherapeutic agents. Twenty male athymic BALB/c-nu/nu mice were randomized into HepG2/nude and HepG2/ADM/nude groups (10 in each group). A cell suspension (either HepG2 or HepG2/ADM) was injected subcutaneously into mice in each group. Tumor growth was recorded, and animals were sacrifi ced 4-5 wk after cell implantation. Tumors were prepared for histology, and viable tumor was dispersed into a single-cell suspension. The IC50 values for a number of chemotherapeutic agents were determined by 2, 3-bis (2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5- carboxanilide inner salt (MTT) assay. Rhodamine-123 retention/efflux and the level of resistance-associated proteins were determined by ? ow cytometry. The mRNA expression of mdr1, mrp and lrp genes was detected using reverse transcriptase polymerase chain reaction (RT-PCR) in HepG2/nude and HepG2/ADM/nude groups. RESULTS: The appearances of HepG2/nude cells were slightly different from those of HepG2/ADM/nude cells. Similar tumor growth curves were determined in both groups. A cross-resistance to ADM, vincristine, cisplatin and 5-fluorouracil was seen in HepG2/ADM/nude group. The levels of P-glycoprotein and multidrug resistance- associated proteins were significantly increased. The mRNA expression levels of mdr1 , mrp and lrp were higher in HepG2/ADM/nude cells.CONCLUSION: ADM-resistant HepG2 subline in nudemice has a cross resistance to chemotherapeutic drugs. It may be used as an in vivo model to investigate the mechanisms of MDR, and explore the targeted approaches to overcoming MDR. METHODS: HepG2 cell cultures were incubated with increasing concentrations of adriamycin (ADM) to develop an ADM-resistant cell subline (HepG2) in nude mice. AIM: To establish a multidrug resistant (HepG2 / ADM) with cross resistance to other chemotherapeutic agents. Twenty male athymic BALB / c-nu / nu mice were randomized into HepG2 / nude and HepG2 / ADM / nude groups Tumor growth was recorded, and animals were sacrifice ced 4-5 wk after cell implantation. Tumors were prepared for histology, and viable tumor was dispersed into a single-cell suspension . The IC50 values ​​for a number of chemotherapeutic agents were determined by 2, 3-bis (2-methoxy-4-nitro-5-sulfophenyl) -2H- tetrazolium-5- carboxanilide inner salt / efflux and the level of resistance-associated proteins were determined b y? ow cytometry. The mRNA expression of mdr1, mrp and lrp genes was detected using reverse transcriptase polymerase chain reaction (RT-PCR) in HepG2 / nude and HepG2 / ADM / nude groups. RESULTS: The appearances of HepG2 / nude cells were slightly different from those of HepG2 / ADM / nude cells. Similar tumor growth curves were determined in both groups. A cross-resistance to ADM, vincristine, cisplatin and 5-fluorouracil was seen in HepG2 / ADM / nude groups. The levels of P The mRNA expression levels of mdr1, mrp and lrp were higher in HepG2 / ADM / nude cells. CONCLUSION: ADM-resistant HepG2 subline in nudemice has a cross resistance to chemotherapeutic drugs. It may be used as an in vivo model to investigate the mechanisms of MDR, and explore the targeted approaches to overcoming MDR.