[Reversal of drug resistance in multidrug resistant tumor cells by an oligomer complementary to the MDR1 gene].
OBJECTIVE
To overcome the multidrug resistance (MDR) in tumor cells.


METHODS
Human drug resistant cell line KB-8-5 was transfected with a synthetic oligodeoxynucleotide complementary to the 5' end region of MDR1 gene (ODN). In vitro drug sensitivity was measured by MTT assay. Intracellular drug concentration was assessed by flow cytometric analysis and expression of P-glycoprotein (Pgp) was determined by immunohistochemistry method.


RESULTS
The administration of ODN for 72 hours increased daunorubicin (DNR) accumulation and decreased Pgp expression in KB-8-5 cells. Incomplete reversal of MDR in the KB-8-5 cells was observed when lipofectin was used to deliver ODN to the cells. Lipofectin enhanced the reversing activity, and approximately 74.43% of the cells lost their resistance to DNR.


CONCLUSIONS
ODN circumvents resistance in the KB-8-5 cells may be ascribed to the reduced expression of Pgp in the cells.
Li
H
H
The First Hospital of Beijing Medical University, Beijing 100034.
Sun
G
G
Lu
W
W
Yu
Z
Z
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D003630:Daunorubicin / Q000378:metabolism / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D009838:Oligodeoxyribonucleotides / Q000235:genetics*; D010714:Phosphatidylethanolamines / Q000378:metabolism; D013997:Time Factors
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D009838:Oligodeoxyribonucleotides; D010714:Phosphatidylethanolamines; C020888:1,2-dielaidoylphosphatidylethanolamine; D003630:Daunorubicin