Chemosensitizing interactions of clofazimine and B669 with human K562 erythroleukaemia cells with varying levels of expression of P-glycoprotein

Differential expression of a permeability glycoprotein (P-gp) in human myeloleukaemia K562 cells grown in the presence of the anti-cancer drug, doxorubicin, gave rise to subclones with varying degrees of resistance to other anti-tumour drugs such as vinblastine and daunorubicin. Subclones K562/MMB, MMG and MMF were produced from the parental (K562/P) cell line via limiting dilution and their MDR nature confirmed with flow cytometry using an MRK 16 monoclonal antibody directed at a surface epitope of the P-gp pump. The pattern of increasing P-gp expression in the series K562/P, MMF, MMG and MMB was paralleled by increasing resistance to vinblastine and daunorubicin. When the subclones were pre-incubated with the chemosensitizing drugs clofazimine and B669, a pattern of increasing reversal of resistance to vinblastine and daunorubicin was seen in the series K562/P, MMF, MMG and MMB.