In this paper, we describe the effect of the inhibitor of farnesyltransferase (FTI-277) on radioresistance induced by the 24-kDa isoform of FGF2 in human cells expressing wild-type RAS. Treatment with FTI- 277 (20 μM) for 48 h prior to irradiation led to a significant decrease in survival of radioresistant cells expressing the 24-kDa isoform (HeLa 3A) but had no effect on the survival of control cells (HeLa PINA). The radio- sensitizing effect of FTI-277 is accompanied by a stimulation of postmitotic cell death in HeLa 3A cells and by a reduction in G2/M-phase arrest in both cell types. These results dearly demonstrate that at least one farnesylated protein is involved in the regulation of the radioresistance induced by the 24-kDa isoform of FGF2. Furthermore, the radiation-induced G2/M-phase arrest is also under the control of farnesylated protein. This work also demonstrates that FTase inhibitors may be effective radio-sensitizers of certain human tumors with wild-type RAS.
ASJC Scopus subject areas
- Radiology Nuclear Medicine and imaging