In Vitro Combined Modality Treatment of Prostate Carcinoma Cells with 17-(allylamino)-17-demethoxygeldanamycin and Ionizing Radiation

Abstract

Background: The effect of 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), a benzoquinone-ansamycin-type Hsp90-inhibitor, on the expression of focal adhesion kinase (FAK) and, when combined with ionizing radiation, on the clonogenicity of prostate cancer cells were determined. Materials and Methods: FAK was analyzed by Western immunoblot. Prostate carcinoma cells were exposed either to 17-AAG alone or combined with a single radiation fraction of 3 Gy. Results: FAK concentrations were reduced by 17-AAG in a time-dependent manner. Treatment with 100 nM 17-AAG for 24 h reduced clonogenicity by 90%. The plot of surviving fraction versus radiation energy dose yielded roughly parallel graphs for solvent- and 17-AAG-treated cells. Conclusion: 17-AAG induced rapid degradation of FAK. A single radiation fraction of 3 Gy did not enhance the dose-dependent drug-effect on survival. In this sequence, the combined effect of both modalities towards clonogenicity was largely additive.