The farnesyltransferase inhibitor FTI-277 suppresses the 24-kDa FGF2-induced radioresistance in HeLa cells expressing wild-type RAS

In this paper, we describe the effect of the inhibitor of farnesyltransfera se (FTI-277) on radioresistance induced by the 24-kDa isoform of FGF2 in hu man cells expressing wild-type RAS. Treatment with FTI-277 (20 mu M) for 48 h prior to irradiation led to a significant decrease in survival of radior esistant cells expressing the 24-kDa isoform (HeLa 3A) but had no effect on the survival of control cells (HeLa 3A), The radiosensitizing effect of FT I-277 is accompanied by a stimulation of postmitotic cell death in HeLa 3A cells and by a reduction in G(2)/M-phase arrest in both cell types. These r esults clearly demonstrate that at least one farnesylated protein is involv ed in the regulation of the radioresistance induced by the 24-kDa isoform o f FGF2. Furthermore, the radiation-induced G(2)/M-phase arrest is also unde r the control of farnesylated protein. This work also demonstrates that FTa se inhibitors may be effective radiosensitizers of certain human tumors wit h wild-type RAS. (C) 1999 by Radiation Research Society.