K. Kawamoto et al., EXPERIMENTAL AND CLINICAL-EVALUATION BY FLOW-CYTOMETRY FOR THE MECHANISM OF COMBINATION THERAPY (CISPLATIN AND PEPLOMYCIN), Cytometry, 13(3), 1992, pp. 307-313
Pharmacologic effects of cisplatin (CDDP) and peplomycin (PEP) on tumo
r cell kinetics were studied both in vitro and in vivo with the aid of
flow cytometry (FCM). Double staining with propidium iodide (PI) and
fluorescein isothiocyanate (FITC)-labeled bromodeoxyuridine (BrdU) was
used to analyze the cell cycle, and the number of viable cells was de
termined with fluorescein diacetate (FDA). Effects of combining the 2
agents were also studied to establish the most effective method of com
bination therapy. Furthermore, these agents were tried clinically on t
he basis of experimental results. Results showed that CDDP exerted its
action at the S and G2M phases in the cell cycle and PEP at the G2M p
hase. Among the combination regimens in the experiments with CDDP, PEP
, and CDDP + PEP as analyzed by FCM, the strongest block on the G2M ph
ase was shown in the one at a 2-day interval, resulting in the most ef
fective killing of the tumor cells. Clinical trial of the combination
therapy showed the same results as the in vitro experiment; the therap
y proved useful for improving the patient's clinical condition and the
results obtained with CT imaging and pathology.