[Sensitivity to etoposide in cultured cells from cervical squamous cell carcinoma]

The anti-cancer effect of Etoposide was tested in in vitro in cultures of cells taken from a squamous cell carcinoma of the uterine cervix (SKG-IIIb). Growth inhibition was tested by the regrowth assay method, inhibition of DNA synthesis by the uptake of 3H-thymidine, and morphological changes by the method of Limburg et al. The concentrations of Etoposide used were similar to the blood levels recommended for clinical use. The regrowth assay showed that the effective concentration of Etoposide for 50% cell kill was 7.5 micrograms/ml in 2-hour and 1.0 microgram/ml in 24-hour cultures. The 3H-thymidine uptake test showed that a concentration of 13 micrograms/ml for 2 hours or of 3.5 micrograms/ml for 24 hours resulted in 50% inhibition of DNA synthesis. Morphological changes were much greater in the 2-hour cultures at the higher concentration of Etoposide than in the 24-hour cultures at the lower concentration. Investigation of the drug sensitivity by cell kinetics disclosed prolongation of the cell cycle occurring after 96 hours at 1.0 microgram/ml and inhibition of cell cycle progression occurring after 24 hours at 10.0 micrograms/ml and after 4 or 8 hours at 50.0 mu/ml. Thus, the anti-cancer effect of Etoposide on SKG-IIIb depends on both the concentration and exposure time and is related to its ability to inhibit cell growth and DNA synthesis and to cause morphological changes in the cancer cells.