Anti-Fas IgM monoclonal antibody enhances apoptosis induced by low-dose cytosine arabinoside

作者：Nakamura S^*; Takeshima M; Nakamura Y; Ohtake S; Matsuda T

来源：Anticancer Research, 1999, 19(1A): 197-204.

• leukemia
• HL60 cells
• cytosine arabinoside
• apoptosis
• Fas

Background: Although low-dose cytosine arabinoside (LD-Ara-C) therapy has been accepted as an effective treatment for patients with acute non-lymphocytic leukemia (ANLL) transformed from myelodysplastic syndromes or elderly patients with ANLL, the anti-leukemic mechanism remains to be resolved. Recently, the potential role of the Fas/Fas ligand system in chemotherapeutic drug-induced apoptosis has been studied. In the present study the relationship between the anti-leukemic effect of LD-Ara-C and the Fas/Fas ligand system was examined. Materials and Methods: The human myeloid leukemia cell line HL60 was treated with LD-Ara-C in combination with anti-Fas IgM MoAb, and apoptosis in the treated cells was estimated by morphological observation, DNA electrophoresis and flow cytometry. Simultaneously, changes in Fas antigen expression on cells treated with LD-Ara-C were investigated. Results: Only limited apoptosis was observed following treatment with LD-Ara-C alone or anti-Fas MoAb alone; however, a synergistic increase in apoptosis was observed by treatment with the MoAb in combination with pretreatment with LD-Ara-C. LD-Ara-C induced a slight but consistent increase in the expression of Fas antigen on the treated cells. Moreover, the expression of Fas antigen was enhanced by repeated administration of LD-Ara-C. Conclusions: These findings suggest the possible involvement of the Fas/Fas ligand system in the anti-leukemic effect of LD-Ara-C therapy.

• 出版日期1999-2