Abstract
The synergistic effect mechanism of Cisplatin (CDDP) and Peplomycin (PEP) therapy was studied in terms of its effect on cell-cycle progression.
Based on the clinical dosing schedule that CDDP administration was followed by PEP after a 48 hours interval, the combination chemotherapy of CDDP and PEP was performed on Ehrlich ascites carcinoma. As a result, a significant synergistic effect was obtained.
After a single administration of CDDP, cell accumulation was first observed in the S phase. After 48 hours, cells accumulated in the G2-M phase, but it was reversible and the original pattern restored 96 hours after the administration. After a single administration of PEP, cell accumulation in the G2-M phase was observed, but it also was reversible and the original pattern restored 48 hours after the administration. On the contrary, irreversible response of a DNA pattern was observed after the combination of CDDP and PEP. The occurrence of debris and decrease in cell number may suggest an induction of intense cytotoxic reaction.
One possible mechanism of the synergistic effect of the sequential combination of CDDP and PEP is as follows. Cell accumulation in the G2-M phase is most significant 48 hours after CDDP administration, and PEP, with preferential cytocidal effect on the cells in the G2-M phase, may exert its cytocidal effect more efficiently when it is timely administered. This mechanism may explain the excellent clinical efficacy obtained by combination chemotherapy in which CDDP was administered prior to PEP.
