Sensitizing effect of the phosphatidylinositol 3-kinase inhibitor wortmannin on thermal neutron irradiation with or without boron compound

Wortmannin, a phosphatidylinositol 3-kinase inhibitor, has been found to be an efficient radiosensitizer. We have investigated the radiosensitizing effect of wortmannin on cell killing against thermal neutrons produced by the Kyoto University Research (KUR) reactor. Wortmannin was added to cells 2 hours before irradiation and removed 16 hours after irradiation. Cells were irradiated by thermal neutrons with or without boron at 0, 10, and 20 ppm. The biological end point of cell survival was measured by colony formation assay. The D0 values of thermal neutrons in different boron concentrations, 0, 10, and 20 ppm were 1.2, 1.1, and 1.0 Gy, respectively. When cells were treated with wortmannin, the D0 values decreased to 0.5, 0.6, and 0.8 Gy at boron concentrations of 0, 10, and 20 ppm, respectively. Wortmannin enhanced cell death against thermal neutron irradiation especially in the absence of boron. Thus, our results suggest that wortmannin may be useful to combine with boron neutron capture therapy (BNCT) treatment when boron uptake by cells is limited.