Objective   To investigate the therapeutic efficacy and the possible action mechanisms of the recombinant adenovirus vector carrying antisense multidrug resistance gene 1 (mdr1) targeting the reverse of α-fetoprotein (AFP+) positive MDR of HepG2R cells.   Methods   After transfection of the recombinant adenoviral vector Adeno-EGFP carrying AFP promoter and EGFP gene into LO2

a normal human liver cell line (AFP-)

HeLa (AFP-)

a human cervical cell line

and HepG2 (AFP+)

the transcription level and the EGFP protein expression were detected by Northern blot and fluorescence microscopy. After the transfection of the recombinant adenovirus vector Adeno-asmdr carrying AFP promoter and antisense mdr1 into HepG2R cells and subcutaneous transplanted tumor carrying HepG2R in nude mice

the reverse activity of HepG2R cells was detected in vivo and in vitro.   Results   The results showed that the EGFP gene and protein were markedly transcribed and expressed in HepG2 cells

however

they were very weak in LO2 or HeLa cells. The results also showed a good transcription ability and AFP-targeting specificity of the recombinant adenoviral vector. RT-PCR showed that the mdr1 was markedly down-regulated at 7 d after transfection. Rhodamine 123 efflux tests showed that the retention of the fluorescence reagent was markedly increased in HepG2R cells at 48 h after transfection. The tumor volume following injection with Adeno-asmdr plus ADM group did not increase

but increased significantly in the PBS and ADM groups (P0.05). A high rate of apoptosis of cells was detected by pathological assay in the treatment group with ADM plus Adeno-asmdr.   Conclusion   The recombinant adenoviral expression vector could express the specific target gene in AFP producing hepatocarcinoma cell and block the mRNA expression of mdr1

down-regulate p-gp170

and reverse MDR. Combined with chemotherapeutic agents

the adeno-asmdr could partly reverse the mdr1 gene expression in vivo. It has a potential value for clinical application.