CHARACTERISTICS OF HARRINGTONINE-RESISTANT HUMAN LEUKEMIA HL-60 CELL

AIM: To study the mechanisms of the resistance to harringtonine (Har) in the HL60 cells. METHODS: Growth inhibition, karyotype analysis, flo w cytometry, Western blotting and polymerase chain reaction. RESULTS: The Har-resistant HL60 cell line, named HR20, showed cross resistance to homoharringtonine, doxorubicin, daunorubicin, vincristine, and colc hicine. The growth doubling time and the cell numbers in G(1) phase we re increased. The accumulation of cellular daunorubicin in the resista nt cells was obviously reduced, but distinctly increased by tetrandrin e and verapamil. The numbers of telocentromeric chromosome increased a nd the chromosomal aberration more occured in the resistant cells. The resistant cells overexpressed multidrug resistant mdr-1 gene and P-gl ycoprotein 150 kDa. CONCLUSION: The Har-resistant HL60 cell strain bel onged to a multidrug resistance strain, overexpressing mdr-1 gene and P-glycoprotein.