Effectiveness of Combined Treatment using X-rays and a Phosphoinositide 3-kinase Inhibitor, ZSTK474, on Proliferation of HeLa cells in vitro and in vivo
ZSTK474 is a novel orally applicable PI3K-specific inhibitor and strongly inhibits cancer cell proliferation. To explore further the antitumor effect of ZSTK474 for future clinical usage, combined effects with radiation were studied. The proliferation of HeLa cells was inhibited by the treatment with X-rays alone or ZSTK474 alone. The combination treatment with X-rays and ZSTK474 applied after 24 h post-irradiation for 8 days remarkably enhanced the cell growth inhibition. The combined effect was also observed for the clonogenic survival with continuous ZSTK474 treatment. Western blotting showed enhanced phosphorylation of Akt and GSK-3beta by X-irradiation, whereas the phosphorylation was inhibited by the ZSTK474 treatment alone. The treatment with ZSTK474 after X-irradiation also inhibited the phosphorylation. Combination of ZSTK474 and X-rays also remarkably inhibited xenograft tumor growth. The combined treatment with X-rays and ZSTK474 had a great therapeutic potential than the radiation or the drug therapy alone both in vitro and in vivo
