Objective: To investigate the reversal effect of antisense oligodeoxynucleotide on human multidrug-resistant leukemic cell line K562/AO2.
Methods: 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.
Results: 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.
Conclusion: (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.