effect of inhibiting survivin expression with antisense oligodeoxynucleotides on sensitivity of hepatocellular carcinoma cell lines hepg2 and hepg2adm to adriamycin background objective survivin deserves attention as a selective target for cancer therapy because it is silenced in differentiated adult tissues but is expressed in a variety of human tumors and is involved in tumorigenesis and chemoresistance antisense oligodeoxynucleotides asodn can be used to inhibit the expression of survivin to induce apoptosis or enhance chemosensitivity of tumor cells this study was to investigate the effect of inhibiting survivin expression with asodn on sensitivity of hepatocellular carcinoma cell lines hepg2 and hepg2adm to adriamycin admmethods the expression of survivin in hepg2 and hepg2adm cells was detected by reverse transcriptionpolymerase chain reaction rtpcr and western blot sensitivities of hepg2 and hepg2adm cells to asodn and adm were detected by mtt assay asodn was transfected into hepg2 and hepg2adm cells expression of survivin was detected by rtpcr synergetic effects of low concentrations of asodn and subtoxic concentrations of adm on hepg2 and hepg2adm cells were detected by isobolography the expression of active caspase3 and cell apoptosis were evaluated by flow cytometryresults mrna level of survivin in hepg2adm cells was 15 folds as that in hepg2 cells protein level of survivin in hepg2adm cells was 18 folds as that in hepg2 cells both hepg2 and hepg2adm cells were sensitive to asodnmediated cytotoxicity in a concentrationdependent manner the 50 inhibitory concentration ic50 of asodn was 31790 nmoll for hepg2 cells and 48074 nmoll for hepg2adm cells the maximal cytotoxicity was observed at 500 nmoll of asodn the inhibitory rate was 7110 in hepg2 cells and 5367 in hepg2adm cells the ic50 of adm was 036 microgml for hepg2 cells and 212 microgml for hepg2adm cells the resistance index was 6 asodn efficiently downregulated mrna level of survivin in both cell lines in a concentrationdependent manner for hepg2 cells with the ic50 of 27193 nmoll the maximal effect of asodn was achieved at a concentration of 400 nmoll at which mrna level of survivin was downregulated by 6912 for hepg2adm cells with the ic50 of 36572 nmoll its maximal effect was achieved at a concentration of 400 nmoll at which mrna level of survivin was downregulated by 6001 asodn in combination with adm synergetically enhanced sensitivity of hepg2 cells to adm by 6 folds and hepg2adm cells by 4 folds combination treatment of asodn and adm gradually enhanced activity of caspase3 and cell apoptosis in a concentrationdependent manner and resulted in caspasedependent cell death in hepg2adm cellsconclusion inhibiting survivin expression with asodn could sensitize hepatocellular carcinoma cells to adm and the combination of asodn and adm may be a reasonable approach for clinical treatment of admresistant hepatocellular carcinoma