Reverse multidrug resistance of hepatocellular carcinoma by suppressing breast cancer resistance protein gene
AIM: To investigate the suppression of breast cancer resistance protein ( BCRP) gene and protein by small interfering RNA ( siRNA) and the restoration of its sensitivity to chemothera-peutic drugs in multidrug-resistant hepatocellular carcinoma cell line HEPG2/ADM. METHODS: BCRP targeted siRNA duplexes were transfected into HEPG2/ADM. The suppression of BCRP gene and protein product was analyzed by RT-PCR and Western blot, respectively. MTT assay was performed to measure the reverse effect of BCRP-siRNA based on the results of IC50. RESULTS: The over-expression of BCRP gene was suppressed efficiently by siRNA. The levels of BCRP mRNA and protein expression in the transfected HEPG2/ADM cells reduced to 22.55% and 37.49% in comparison with those in the controls, respectively. Their resistance to ADM was reversed by 3.55 folds, which indicated the restoration of its sensitivity to drugs. CONCLUSION: The sequence specific RNAi inhibits BCRP mRNA and protein expression in the HepG2/ADM cells. It may reverse multidrug resistance phenotype and thus provide promising therapeutic modalities in the treatment of hepatocellular carcinoma (HCC).
drug resistancemultiplebreast cancer resistance proteinRNA interferencecarcinomahepatocellular
NETL
NSTL
万方数据
维普
