[Inhibition of multidrug resistance gene 1 expression in glioma by antisense oligodeoxynucleotides].
OBJECTIVE
To investigate the effectiveness of phosphorothioate multidrug resistance gene 1 (MDR1) antisense oligodeoxynucleotides (MDR1-AS) suppressing MDR1 expression in multidrug-resistant glioma cell line C6/adr.


METHODS
The glioma cell line C6/adr served as the tested model in vitro, MDR1-AS (5'-CTCCATCACCACCTC-3'), complementary to the -9- +6 sequence of first exon, was synthesized and phosphorothioate-modified. As control of sequence specificity, MDR1-S (5'-GAGGTGGTGA TGGAG-3') was used. Both antisense and sense oligodeoxynucleotides were transduced to C6/adr cells by lipofectin. The cytotoxity of MDR1-AS was tested using morphological observation and 3- (4,5-dimethylthiazol-2-yl) -2, 5-diphenyl tetrazolium bromide assay. Semi-quantitative reverse transcription polymerase chain reaction was used to monitor the expression levels of the MDR1 mRNA in the different groups. The positive rate of the MDR1 gene product P glycoprotein (P-gp) was determined by flow cytometry assessment.


RESULTS
No cytotoxicity of MDR1-AS was observed. The MDR1 mRNA expression level was decreased from 106% to about 30.44% 48 h after MDR1-AS treatment. The P-gp positive rate of MDR1-AS treated C6/adr cells decreased from 100% to 32.77%, with that of C6/adr cells considered as 100%.


CONCLUSIONS
MDR1-AS can effectively inhibit MDR1 expression in the C6/adr cell line at both the mRNA and protein level, and may be an alternative treatment of drug-resistant gliomas.
Kong
Jian-xin
JX
Department of Neurosurgery, the Second Affiliated Hospital of Shandong University, Jinan 250033, China. kongjianxin@hotmail.com
Song
Qian
Q
Liu
Yan-peng
YP
Wang
Cheng-wei
CW
Zhang
Qing-lin
QL
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005910:Glioma / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D020319:Oligodeoxyribonucleotides, Antisense; D012333:RNA, Messenger