Taxol sensitizes human astrocytoma cells to radiation.
Taxol is a chemotherapeutic drug which acts by stabilizing microtubules, preventing normal mitosis and resulting in a block of the cell cycle at G2 and M. The drug is isolated from the yew, Taxus sp. L., and is currently being evaluated in a series of Phase II and Phase III clinical trials. Taxol blocks cells in the most radiosensitive phases of the cell cycle and thus could act as a cell cycle-specific radiosensitizer. We report the results of combined taxol-radiation exposures in the human Grade III astrocytoma cell line, G18. Taxol is a potent inhibitor of G18 cell division; a concentration of 10 nM is cytostatic for a cell population observed for at least two doubling times. Cell survival curves for G18 cells showed a significant concentration-dependent interaction between taxol and radiation. Treatment of G18 cells with a fixed taxol concentration and radiation dose showed the interaction to be dependent on the duration of taxol exposure and consequently the fraction of cells in the G2 or M phase of the cell cycle. The sensitizer enhancement ratio for 10 nM taxol at 10% survival is 1.8 and, for 1 nM taxol, it is 1.2. These results suggest that appropriate combinations of taxol have a more than additive interaction in human tissue culture and may have a role in clinical protocols.
Tishler
R B
RB
Department of Radiation Oncology, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
Geard
C R
CR
Hall
E J
EJ
Schiff
P B
PB
D000470:Alkaloids / Q000494:pharmacology*; D001254:Astrocytoma / Q000532:radiotherapy*; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D017239:Paclitaxel; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000470:Alkaloids; D011838:Radiation-Sensitizing Agents; D017239:Paclitaxel