Abstract
We examined the effects of an inhibitor (LY294002) of PI3K on radiation or hyperthermic sensitivity. We used two human non-small cell lung cancer cell lines (H1299/wtp53 and H1299/mp53) transfected with wild and mutant p53 genes. We measured the sensitivity to X-ray and heat by colony formation assay and frequency of apoptosis by Hoechst staining and accumulation of apoptosis-related proteins by Western blotting analysis. LY294002 (final concentration at 40 mM) was added to the culture medium at 1 hr before X-ray or hyperthermia treatment. The addition of LY294002 enhanced the sensitivity of X-ray or hyperthermia and accumulation of survivin independently on p53 genotype. The induction of hsp70 after hyperthermia was inhibited by LY294002. These results suggested that LY294002 sensitized radiosensitivity and thermosensitivity through the depression of survivin and hsp70-induction. Since we demonstrated that another PI3K inhibitor of wortmannin did not sensitize the thermosensitivity, on the contrary, it is suggested that there are some differences in the modality of protein phosphorylation between radiosensitivity and thermosensitivity. [J Radiat Res 44:447 (2003)]
