Effects of docetaxel in combination with radiation on human head and neck cancer cells (ZMK-1) and cervical squamous cell carcinoma cells (CaSki ).
The purpose of this study was to determine, as we did for paclitaxel, the cytotoxic and radiosensitizing potential of docetaxel in human head and neck cancer cells (ZMK-1), and in cervical squamous cell carcinoma cells (CaSki). ZMK-1 cells were incubated with docetaxel for 3, 9 or 24 hr before irradiation and 24 hr after irradiation. CaSki cells were incubated with docetaxel 24 hr before and after irradiation. For ZMK-1 cells, the docetaxel concentrations (0.7, 0.7 and 0.35 nM) were determined to obtain approximately equivalent cell survival at the different incubation times (3, 9 and 24 hr, respectively). For CaSki cells, the necessary concentration of docetaxel was 0.07 nM. Radiation doses were given from 0 to 7 Gy. Cell survival was measured by a standard clonogenic assay after a 9-day incubation. Flow cytometry was used to measure the capacity of docetaxel to accumulate cells in the G2/M phase of the cell cycle. We observed a weak accumulation of cells in the G2/M phase for the ZMK-1 cells and a pronounced accumulation for CaSki cells. For docetaxel incubation before irradiation, the isoeffect enhancement ratios for ZMK-1 cells determined at the 37% survival level were 1.18, 2.01, and 2.40 for pre-incubation at 3, 9 and 24 hr, respectively; for CaSki cells the ratio was 1.44. For a docetaxel incubation of 24 hr after irradiation, the isoeffect enhancement ratios determined at the 37% survival level were 1.54 and 1.17 for the ZMK-1, and CaSki cells, respectively. A radiosensitizing effect of docetaxel could be demonstrated unambiguously in the two cell lines used. In contrast to our previously published results with paclitaxel, docetaxel seems to be a better radiosensitizer than paclitaxel.
Department of Radiotherapy and Radiation Oncology, University of Göttingen, Robert-Koch-Str. 40, D 37075 Göttingen, Germany. opradie@gwdg.de
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O
Pradier
M
M
Rave-Fränk
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J
Lehmann
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E
Lücke
O
O
Boghun
C F
CF
Hess
H
H
Schmidberger
D002294:Carcinoma, Squamous Cell / Q000628:therapy*; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D006258:Head and Neck Neoplasms / Q000628:therapy*; D006801:Humans; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D011836:Radiation Tolerance; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D011878:Radiotherapy; D043823:Taxoids; D013997:Time Factors; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000628:therapy*
D011838:Radiation-Sensitizing Agents; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel