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Mechanisms of drug resistance of two cell lines of human chronic promyelocytic leukemia K562, resistant to DNA topoisomerase Ii inhibitors adriamycin and etoposide

Meliksetian, M.B.; Berezkina, E.V.; Pavlenko, M.A.; Grinchuk, T.M.

Tsitologiia 41(7): 615-621

1999

ISSN/ISBN: 0041-3771
PMID: 10496023
Document Number: 500985
Mechanisms of drug-resistance in two K562 cell lines selected for adriamycin and etoposide resistance (K562-ADR and K562-VP16, respectively) were studied. In K562-ADR cells, overexpression of mdr 1 gene and two-fold reduction of topoisomerase II alpha mRNA content were found, while topoisomerase II beta expression remained unchanged, compared to the parental cell line. Antiapoptotic bcl-2 mRNA level was four-fold decreased in K562-ADR cells, while the expression of other members of bcl-2 family was unaffected. In K562-VP16 cells five-fold reduction of topoisomerase II alpha expression was found with the absence of mdr 1 gene overexpression. The expression of antiapoptotic bcl-2 and proapoptotic bax genes was reduced in K562-VP16 cell line, while the content of bcl-2 mRNA was increased. Cytogenetic analysis of K562-VP16 cells revealed morphological changes in their cell karyotype and susceptibility of these cells to spontaneous polyploidization. Possible effects of etoposite on mitotic control in K562-VP16 cells are discussed.

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