Effects of paclitaxel in combination with radiation on human head and neckcancer cells (ZMK-1), cervical squamous cell carcinoma (CaSki), and breastadenocarcinoma cells (MCF-7)

Background and purpose: The anticancer drug paclitaxel, a natural product f rom Taxus brevifolia, is a microtubule-stabilising agent, which has been sh own to block different cells in the G2/M phase of the cell cycle and so mod ulate their radioresponsiveness. We investigated the radiosensitizing poten tial of paclitaxel in human head and neck cancer cells (ZMK-1), in cervical squamous cell carcinoma cells (CaSki) and in breast adenocarcinoma cells ( MCF-7). Methods: ZMK-I cells were incubated with paclitaxel for 3, 9, or 24 h before irradiation. ZMK-1-, CaSki- and MCF-7 cells were incubated with p aclitaxel for 24 h after irradiation. The paclitaxel concentration (70 nM. 7 nM, 0.7 nM) was chosen to obtain equivalent toxicity at the different inc ubation times (3 h, 9 h, 24 h respectively). Radiation doses were from 0 to 8 Gy. Cell survival was measured by a standard clonogenic assay after a 9- day incubation. Flow cytometry was used to measure the capacity of paclitax el to cause accumulation of cells in the G2/M phase of the cell cycle. Resu lts: Paclitaxel alone was cytotoxic in a time- and concentration-dependent manner. Up to 36% of the ZMK-1 cells accumulated in G2/M after treatment fo r 24-36 h. If the cells were incubated with paclitaxel before irradiation t he isoeffect enhancement ratios for ZMK-1 cells, determined at the 37% surv ival level? were 0.81, 1.48 and 1.15 for 3-h, 9-h, and 24-h pre-incubations respectively. For a paclitaxel incubation of 24 h after irradiation, the i soeffect enhancement ratios, determined at the 37% survival level, were 0.7 2, 0.76 and 1.2 for the ZMK-1, CaSki, and MCF-7 cells respectively. Conclus ion: In the three cell lines no radiosensitizing effect of paclitaxel could be demonstrated unambiguously. The use of asynchronized cells or the suppo rt of cellular repair mechanisms while the cells are blocked in G2/M could partly explain the results.