[Mechanisms of drug resistance of two cell lines of human chronic promyelocytic leukemia K562, resistant to DNA topoisomerase II inhibitors adriamycin and etoposide].
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.
Meliksetian
M B
MB
Institute of Cytology, Russian Academy of Sciences, St. Petersburg.
Berezkina
E V
EV
Pavlenko
M A
MA
Grinchuk
T M
TM
D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D017931:DNA Primers; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005047:Etoposide / Q000494:pharmacology*; D006801:Humans; D020014:K562 Cells; D007621:Karyotyping; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D059005:Topoisomerase II Inhibitors; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D017931:DNA Primers; D004791:Enzyme Inhibitors; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D059005:Topoisomerase II Inhibitors; D051028:bcl-2-Associated X Protein; D005047:Etoposide; D004317:Doxorubicin