Quantification of apoptosis induction by doxorubicin in three types of human mammary carcinoma spheroids.

BACKGROUND

Apoptosis, also termed programmed cell death, is an active form of cellular degradation in contrast to the passive, inflammatory necrosis. Triggering apoptosis in tumor cells is a significant aim of chemotherapeutic treatment.

MATERIALS AND

METHODS

In this investigation the rate of apoptosis in human mammary carcinoma cell spheroids and monolayers was quantified following treatment with doxorubicin using various concentrations and incubation times. These data were compared with results of standardized clonogenicity assays, spheroid volume growth curves, and flowcytometric cell cycle analysis and BrdU-labeling.

RESULTS

Whereas spheroid volume growth and cellular clonogenicity were in excellent accordance with the well-established chemosensitivity of the three cell lines, the incidence of apoptosis did not reflect the different susceptibility of the cell lines to doxorubicin in a systematic way. On the other hand, theoretical considerations showed that the relatively low proportion of apoptosis can account for the relatively large decrease in spheroid volume, as observed in doxorubicin-treated T47D spheroids.

CONCLUSIONS

The experimental data suggest that suppression of apoptosis is not an obligatory feature of multi-drug resistant cell lines, and that resistance is rather correlated with an increase in DNA-synthesis.