Abstract
To investigate the possibility of reversion of multidrug resistance in lung adenocarcinoma-resistant cell line A549/R by antisense strategy including mdr1 antisense oligodeoxynucleotide and Ribozyme. The target points, -9 to +6 in mdr1 cDNA sequence and GUC at 880 site of mdr1 mRNA were selected. Phosphorothioate antisense oligodeoxynucleotide and DNA of plasmid expressing anti-mdr1 Ribozyme(pHβApr-1 neo/mdr1-Rb )corresponding to above target points were transfered into A549/R cell by lipofectin. The expression of mdr1 mRNA and Pgp, cellular rhodamine accumulation and sensitivity to doxorubicin were detected respectively in transfered cells and control cells by RT-PCR, flow cytometry, rhodamine test and MTT. Treatment of A549/R cell with antisense oligodeoxynucleotide and Ribozyme led to decrease of mdr1 mRNA and Pgp expression, increase of rhodamine cellular accumulation, and 20-180 fold increase of sensitivity to doxorubicin compared to control cell. The mdr1 antisense oligodeoxynucleotide and Ribozyme are possessed with powerful effect on reversion of MDR in lung adenocarcinoma-resistant cell A549/R by inhibiting mdr1 transcription, cleaving mdr1 mRNA and decreasing Pgp expression. Antisense strategy is a promising method of reversion of multidrug resistance in lung cancer.
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