γ-secretase Inhibitor Enhances Antitumor Effect of Radiation in Notch Expressing Lung Cancer

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We discovered that the antitumor effect of combining GSI(-secretase inhibitor) and radiation was dependent on treatment schedule. GSI administration after radiation had the greatest growth inhibition of lung cancer in vitro and in vivo. We showed that the combination induced apoptosis of lung cancer cell lines through the regulation of MAPK and Bcl-2family proteins. Furthermore, activation of Notch after radiation was ameliorated by GSI administration, suggesting that treatment with GSI prevent Notch-induced radiation resistance.