[Experimental studies on combination chemotherapy based on cell cycle analysis]

Based on Peplomycin-induced cell cycle distribution analyzed by a flow-cytemetry using HeLa S-3 and SNG-M cells in vitro, we investigated reasonable periods and kinds of drug combined with pepleomycin (PEP). Changes in both the PEP treatment time and dosage produced a redistribution which decreases the number of cells in the G1 phase and increased the number of cells in the S and G2-M phases. The period with the maximum number of cells in the S phase was 12 hours in the HeLa S-3 and 16 hours in the SNG-M and, that in the G2-M phases, 16 hours in the HeLa S-3 and 22 hours in the SNG-M after the treatment. In the combination of the pep with CIS-DDP 4-hydroperoxy cyclophosphamide Adriamycin (ADR) and ACNU, the cytotoxic potency of the four drugs were CIS-DDP greater than 4-Hydroperoxy cyclophosphamide greater than ADR greater than ACNU in the HeLa S-3 and 4-Hydroperoxy cyclophosphamide greater than CIS-DDP greater than ADR greater than ACNU in the SNG-M. This suggests that the Cis and 4-Hydroperoxy cyclophosphamide were adequate for the combination with the PEP. The period of the combination should be at the time of the greatest accumulation of cells in the G2-M phase, because the pep effectively produced the G2-M partial synchronization. These results suggest that the combination chemotherapy should be based on the analysis of the cell cycle.