[Cell cycles of cancer cells and chemotherapy--flow cytometric observation of the effects of chemotherapeutic agents on cell kinetics of cultured human lung cancer cells].

The necessity to assess the influence of chemotherapeutic agents on cell cycle kinetics has been stressed for development of effective cancer chemotherapy. Effects of these agents on cell cycle progression in cultured human lung cancer cells, PC-3 (adeno) and PC-6 (small cell), were studied by flow cytometry (FCM) with computer analysis. DNA distributions of the cells stained with propidium iodide were expressed numerically. Firstly the influence of adriamycin (ADR), then methotrexate (MTX), and finally, sequential combined chemotherapy with ADR and MTX on cell cycle kinetics were examined. The results are summarized as follows. Exposure to ADR induced concentration dependent cell killing effect in PC-3 and PC-6, while exposure to MTX showed mainly time dependent cell growth inhibition. By FCM, difference of effect of ADR between those two cell types was certified. Namely, in PC-3 low ADR concentration lead to G2 accumulation with decrease of G0/G1, polyploization, and high ADR concentration to S accumulation due to S-G2/M delay. Furthermore, in the highest ADR concentration (10 micrograms/ml), G1, G1-S boundary accumulation were observed. On the contrary, exposure of PC-6 to ADR remained to show only G2 accumulation with a slight decrease of G0/G1. Exposure of PC-6 to MTX lead to G2/M decrease with delay of G0/G1-S progression followed by S accumulation which was ascribed to delay of S-G2/M progression. Sequential combined chemotherapy showed superiority of MTX-ADR to ADR-MTX and other regimens in cytocidal effect, and the difference might be attributable to induction of partial synchronization to G0/G1-S boundary with MTX exposure. It was emphasized that FCM is a indispensable method for analysis of the influence of chemotherapeutic agents on cell cycle kinetics.