Objective: To investigate the possibility of reversion of multidrug resistance (MDR) in lung adenocarcinoma-resistant cell line A549/R by mdr1 antisense oligodeoxynucleotide.
Methods: A 15-mer phosphorothioate antisense oligodeoxynucleotide (ATCCATCCCGACCTC), complementary to -9 approximately + 6 in mdr1 cDNA sequence, was synthesized. Meanwhile, sense sequence (GAGGTCGGGATGGAT) was taken as control. Both antisense and sense oligodeoxynucleotides were transduced to A549/R cell line by lipofectin. The mdr1 mRNA, expression of Pgp, cellular rhodamine accumulation and sensitivity to daunorubicin were detected in antisense and sense oligodeoxynucleotides treated cells, using RT-PCR, flow cytometry, rhodamine test and MTT method.
Results: Treatment with antisense oligodeoxynucleotide in A549/R cells led to a decrease in mdr1 mRNA and Pgp expression, an increase in rhodamine cellular accumulation, and a 20-fold increase of sensitivity to doxorubicin compared with those treated with sense oligodeoxynucleotide or control cells.
Conclusion: The mdr1 antisense oligodeoxynucleotide possesses an effect of reversing MDR in lung adenocarcinoma-resistant cell A549/R by inhibiting mdr1 transcription and Pgp expression.