[Reversal of multidrug resistance in lung adenocarcinoma-resistant cell line A549/R by mdr1 antisense oligodeoxynucleotides in vitro].
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.


CONCLUSIONS
The mdr1 antisense oligodeoxynucleotide possesses an effect of reversing MDR in lung adenocarcinoma-resistant cell A549/R by inhibiting mdr1 transcription and Pgp expression.
Chen
L
L
Department of Pulmonary Medicine, General Hospital of PLA, Beijing 100853, China.
Liu
Y
Y
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D000230:Adenocarcinoma; D004247:DNA / Q000032:analysis; D003630:Daunorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D005456:Fluorescent Dyes / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D012235:Rhodamines / Q000378:metabolism; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005456:Fluorescent Dyes; D020319:Oligodeoxyribonucleotides, Antisense; D012333:RNA, Messenger; D012235:Rhodamines; D004247:DNA; D003630:Daunorubicin