Host: The Japan Radiation Research Society
Co-host: Asian Association for Radiation Research
The effects of amrubicin (AMR) and its active metabolite, amrubicinol (AMROH), on the sensitivity of human lung adenocarcinoma A549 cell line to hyperthermia at 44°C were investigated, and the cell phase response and the kinetics of apoptosis / necrosis were analyzed. Sequential treatments with AMR (2.5 µg/ml) or AMROH (0.02 µg/ml) prior to 44°C hyperthermia resulted in additive thermo-enhancement effect by reducing not only survival but was shoulder wide. The thermo-enhancement effects of DNA topoisomerase II inhibitor, AMR, AMROH, adriamycin (ADM) and etoposide (VP-16) on 44°C hyperthermia were compared, and these agents exhibited comparable thermo-enhancement effects. The cell phase response with each agent were studied. It is reported that ADM is sensitive to S phase and VP-16 is sensitive to G2-S phase. In our study using synchronized A549 cells, AMR or AMROH did not elicit cell phase responses irrespective of the concentration. The incidence of apoptosis was observed at 48 and 72 h after AMROH for 4 h, 44°C hyperthermia for 35 min alone or the combined treatment, which apoptosis was not significantly induced after any treatment. Furthermore, the incidence of necrosis was examined as well as apoptosis. The necrosis induced after the combined treatment was circa 3 times higher than that in either of the single treatments.
