Background. Several recent studies have suggested radiosensitizing effects of paclitaxel, a microtubular inhibitor. To test the universality of this finding, the interaction between paclitaxel and radiation treatment of cell lines derived from three common human carcinomas MCF-7 (breast cancer); DUT-145 (prostate cancer); and HT-29 (colon cancer) was evaluated. The study focused on the ability of paclitaxel to block cells at the G2-M phase of the cell cycle and potentially enhance the radiation sensitivity of the cells.
Methods. All cell lines were exposed to three different clinically achievable paclitaxel concentrations ranging from 2 nM to 25 nM. Paclitaxel pretreatment for 1 2 and 24 hours before radiation was tested in all three cell lines. The radiation dose ranged from 0 to 8 Gy delivered in a single fraction. Cellular survival after treatment with paclitaxel and/or radiation was determined by clonogenic assay. Cell cycle distribution as determined by flow cytometry was performed after various dose-time combinations of paclitaxel.
Results. Cytotoxicity studies with paclitaxel alone demonstrated a time-dependent and dose-dependent sur- vival relationship for all three cell lines. Resultant surviving fractions were in the range of 5 to 90% after 24hour exposure to paclitaxel alone. The interaction between paclitaxel and radiation was primarily additive in each of the three cell lines for all paclitaxel dose-time combinations studied. Flow cytometric analysis failed to