Further mechanistic unravelling of the influence of the cell cycle effects on the radiosensitising mechanism of vinflunine, in vitro.
OBJECTIVE
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.


METHODS
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.


CONCLUSIONS
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.
Simoens
Cindy
C
Laboratory of Cancer Research and Clinical Oncology, Department of Medical Oncology, University of Antwerp (UA/UZA), Universiteitsplein 1, 2610, Wilrijk (Antwerp), Belgium. cindy.simoens@ua.ac.be
Pauwels
Bea
B
Vermorken
Jan B
JB
Pattyn
Greet G O
GG
Lambrechts
Hilde A J
HA
Breillout
Fabienne
F
Lardon
Filip
F
D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D005434:Flow Cytometry; D005720:Gamma Rays; D006801:Humans; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D013997:Time Factors; D050257:Tubulin Modulators / Q000494:pharmacology*; D014747:Vinblastine / Q000494:pharmacology*
D011838:Radiation-Sensitizing Agents; D050257:Tubulin Modulators; D014747:Vinblastine