RELATIONSHIP BETWEEN BIOLOGICAL EFFECTS AND UPTAKE OF C-MYC ANTISENSE OLIGONUCLEOTIEDS IN ERYTHROLEUKEMIC CELLS

YUAN XJ, ZHOU M, LUO CH, LIAO QK

Pediatric Department, 2nd University Hospital, Sichuan University (Huaxi Campus), Chengdu, China

Objective: To study the relationship between biological effects and cellular uptake of c-myc antisense oligonulceotides and their cationic liposome complexes in human erythroleukemic K562 cells.

Methods: The biological activity of c-myc antisense olignoucleotides and their liposome complexes was determined by counting the cell number using MTT assay, while their cellular uptake conditions were measured by lazer confocal scanning technique.

Results: Proliferation of K562 cells was inhibited by antisense S-oligo and PS-oligo, while antisense P-oligo and sense S-oligo were ineffective. In oligo-liposome complexes group, inhibiting degree of K562 proliferation was greatly increased comparing with oligo group. In confocal fluorescence microscopic study, uptake of S-oligo, PS-oligo and P-oligo was observed to be time-dependent and mainly distributed on the cell surface and in the cytoplasm, when complexed with liposomes, cellular uptake was significantly increased and the fluorescence was located mainly in the nucleus.

Conclusions: Control of the intracellular uptake and localization of antisense oligo nucleotides in K562 cells by cationic liposomes may lead to a more efficient antisense activity.

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