SELECTIVE REVERSAL OF DRUG-RESISTANCE IN DRUG-RESISTANT LUNG ADENOCARCINOMA CELLS BY TUMOR-SPECIFIC EXPRESSION OF MDR1 RIBOZYME GENE MEDIATED BY RETROVIRUS

According to the fact that CEA gene expressed only in lung adenocarcin oma and not in normal lung cells, a retroviral vector (pCEAMR) was con structed which carried the CEA promoter coupled to MDR1 ribozyme gene. pCEAMR was introduced into drug-resistant lung adenocarcinoma cells G AOK with CEA expression and HeLaK without CEA expression; the expressi on of pCEAMR and drug resistance in the infected cells were analyzed i n vitro and in vivo; pCEAMR expressed only in CEA-producing GAOK cells and not in non-CEA-producing HeLa cells. The drug resistance to doxor ubicin (DOX) decreased 91.5% in the infected GAOK cells and did mt cha nge in the infected HeLa cells. In nude mice, DOX could obviously inhi bit the growth of the infected GAOK tumors, and had no effect on the g rowth of the infected HeLa cells. These results indicated that MDR1 ri bozyme gene regulated by CEA promoter expressed only in human adenocar cinoma cells and reversed their drug resistance selectively. This gene -drug therapy might serve as an effective treatment method for patient s with CEA-producing lung cancers which was usually refractory to conv entional chemotherapy.