In vitro study of a paclitaxel-radiotherapy combination on a human epidermoid tumor cell line]

PURPOSE: Paclitaxel is an agent which stabilizes microtubules, and has been shown to block different cells in the G2/M phase of the cell cycle and thus to modulate their radioresponsiveness. We investigated the radiosensitizing potential of paclitaxel in human head and neck cancer cells. MATERIALS AND METHODS: ZMK-1 cells were incubated with paclitaxel for 3, 9, or 24 h before or during 24 h after irradiation. Paclitaxel concentrations of 70 nM, 7 nM, and 0.7 nM were chosen to obtain equivalent toxicity at the different incubation times: 3 h, 9 h, and 24 h, respectively. Radiation doses ranged from 0 to 8 Gy using 60Co source. Cell survival was measured by a standard clonogenic assay after a 9-day incubation. Flow cytometry was used to measure the capacity of paclitaxel to accumulate cells in the G2/M phase. RESULTS: Paclitaxel alone possessed cytotoxicity dependent on time and concentration. There was a total of 40% of cells accumulated in G2/M after 24-36 h. When combined with radiation, the 9 h preincubation resulted in a radiosensitization. The 3 h pre-incubation as well as the 24 h post-incubation resulted in an infra-additive effect. CONCLUSION: In our cells a radiosensitizing effect of paclitaxel could not be demonstrated unambiguously. The blockage of the cells in the G2/M phase is not the only mechanism to explain the potential radiosensitization of paclitaxel.