The effect of the Fas/FasL pathway during chemotherapeutic drug-induced apoptosis of leukameic cells

Abstract

The mechanism of chemotherapeutic drug-induced apoptosis in leukaemic cells was studied to further investigate whether Fas/FasL system was involved in apoptosis induced by chemotherapeutic drugs and assess their effects when used in combination with soluble FasL (sFasL). The expression of Fas on human leukaemic cell lines K562, HL-60 and U937 treated with daunorubicin (DNR) or cytosine arabinoside (Ara-C) was detected by using flow cytometry. The activities of sFasL, DNR and Ara-C inducing apoptosis of leukaemic cells, in the absence or presence of neutralizing anti-Fas IgG antibody, were detected by using flow cytometry and TUNEL. The results showed that flow cytometric profiles of K562, HL-60 and U937 cells treated with DNR or Ara-C failed to show any significant increase in Fas expression over 18 h (P>0.05). Anti-Fas monoclonal antibody (IgG) could not block the apoptosis in leukaemic cells induced by DNR or Ara-C, but could block the apoptosis induced by sFasL. A role of sFasL in a cytotoxic synergistic effect when used in combination with chemotherapeutic drugs was revealed. It was concluded that chemotherapeutic drug-induced apoptosis in human leukaemic cells (UG37, HL-60) is independent of the Fas/FasL system, but combination of sFasL and drug treatment produces a synergistic cytotoxic effect on human luekaemic cells.

Keywords

apoptosis / Fas ligand / leukaemic cells / cytotoxic

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