Abstract
The effects of the heat shock protein 90 (Hsp90) inhibitor were examined on the radiosensitivity and signal transduction pathways in human cells. Cell lines were incubated for 16 hr in medium containing Hsp90 inhibitor geldanamycin The cells were then irradiated with X-rays and incubated with the drug for a further 8 hr. Geldanamycin sensitized human tumor cells, but not normal cells, to radiation. 17AAG, a geldanamycin derivative, also sensitized human squamous carcinoma cell lines. It was found that 17AAG reduced the expression of Akt and phosphorylated Akt. In addition, the ratio of apoptotic cells increased in tumor cells after a combination of 17AAG and X-rays. A similar results were obtained in tumor cells grown as multicellular spheroids, in vitro human tumor model. In conclution, targeting Hsp90 with 17AAG provides a promising strategy for radiosensitization of radioresistant carcinoma.
