[Effects of antisense oligodeoxynucleotides targeting multidrug resistance gene on resistant cell line K562/ AO2]

To investigate the reversal effect of antisense oligodeoxynucleotide on human multidrug-resistant leukemic cell line K562/AO2.

Antisense oligodeoxynucleotides (AOD) targeting-6 approximately 9 sites of exon 2 in human multidrug resistance gene(mdr-1), one of which is sequence-strict-complied and linked with polyethyleneglycol (PEG) at 5' end (AP, 15 mer), the other lacks nucleotide complied site-1 (AP', 14mer), were synthesized. AP, AP' and verapamil were simultaneously added to human mdr-1-mRNA positive leukemia cell line K562/AO2 and, mdr-1-mRNA and p170 were detected. AS' and AP'were labelled by FITC and designated as ASF' and APF', respectively. In addition, the intracellular concentration of them was detected by FACS.

AP' significantly enhanced the sensitivity of K562/AO2 to DOX, down-regulated the expression of mdr-1 and MRP-mRNA and p170, elevated the intracellular concentration of the two AOD, while AP had no effect. The uptake of APF' was significantly higher than that of ASF' in K562/AO2, and the fluorescence was observed in the plasma and nuclear of K562/AO2 cells.

(AOD targeting mdr-1 promoted the drug sensitivity of drug-resistant tumor cells. 2 AOD had no cytotoxicity to tumor cells. 5 Low molecule PEG enhanced significantly the uptake of AOD by tumor cells.