INDUCTION OF APOPTOSIS IN HL60 LEUKEMIC-CELLS BY ANTICANCER DRUGS IN COMBINATION WITH ANTI-FAS MONOCLONAL-ANTIBODY

Some anticancer drugs kill tumor cells through the mechanism of apopto sis. Fas antigen has been generally noticed as an apoptosis-signalling receptor molecule on the surface of different cells. Recently it has become clear that some tumor cells express Fas antigen on their surfac e and apoptosis is induced in those cells by IgM-anti-Fas monoclonal a ntibody (IgM-anti-Fas MoAb). If it is possible to induce apoptosis in tumor cells effectively by anticancer drugs in combination with IgM-an ti-Fas MoAb, then we may be able to develop a new strategy for cancer chemotherapy. HL60 human leukemic cell line was incubated with antican cer drugs adriamycin (ADM) or cytosine arabinoside (Ara-C) at differen t doses alone and in combination with IgM-anti-Fas MoAb. We then obser ved the morphologic changes of tumor cells, the DNA fragmentation by a garose gel electrophoresis, and the changes in the amount of Fas antig en expression in their cell surface by using flow cytometry. In ADM- o r Ara-C-treated tumor cells, apoptotic cells increased in number time- and dose-dependently. By the combination of ADM or Ara-C with IgM-ant i-Fas MoAb, the induction of apoptosis in HL60 cells was enhanced sign ificantly. The DNA electrophoresis supported those results. The amount of Fas antigen expression was slightly increased only in cells treate d with a low dose of Ara-C, not in others. Our results suggest that ap optosis is a major process of leukemic cell death induced by anticance r drugs. Furthermore, it has become clear that the combination of anti cancer drugs with IgM-anti-Fas MoAb enhances leukemic cell death throu gh apoptosis in vitro, though the mechanism remains to be resolved.