TY - JOUR T1 - Further mechanistic unravelling of the influence of the cell cycle effects on the radiosensitising mechanism of vinflunine, in vitro. JF - Cancer Chemother Pharmacol Y1 - 2008 A1 - Cindy Simoens A1 - Bea Pauwels A1 - Jan B Vermorken A1 - Greet G O Pattyn A1 - Hilde A J Lambrechts A1 - Fabienne Breillout A1 - Filip Lardon KW - Cell Cycle KW - Cell Line, Tumor KW - Cell Survival KW - Flow Cytometry KW - Gamma Rays KW - Humans KW - Radiation-Sensitizing Agents KW - Time Factors KW - Tubulin Modulators KW - Vinblastine AB -

PURPOSE: Vinflunine is an innovative microtubule inhibitor belonging to the vinca alkaloid class that possesses radiosensitising properties, which could lead to promising activity in chemoradiation studies in the clinic.

METHOD: In the current study, different incubation times with vinflunine, immediately before radiation and different time intervals between vinflunine treatment and radiation were investigated, in vitro, using four different human tumour cell lines differing in cell type and p53 status. Results were correlated with the cell cycle distribution at the moment of radiation, in order to elucidate the role of cell cycle perturbations caused by vinflunine on its radiosensitising effect.

RESULTS: Radiosensitisation was observed in all cell lines, and maximal radiosensitisation was both cell line- and schedule-dependent. The cell cycle distributions were cell line-dependent also, and when correlated with the observed radiosensitising effects could explain many (but not all) of the radiosensitising properties of vinflunine.

CONCLUSION: The cell cycle perturbations caused by vinflunine may definitely have an impact on its radiosensitising potential, but other factors must play a role because of some unaccountable differences between cell cycle distribution and the radiosensitising potential.

VL - 62 CP - 2 M3 - 10.1007/s00280-007-0587-4 ER -