| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Outline of Final Research Achievements |
Inhibition of Notch by gamma-secretase inhibitor (GSI) has been shown to have an antitumor effect in Notch expressing non-small cell lung cancer (NSCLC) and induce apoptosis through modulation of Bcl-2 family proteins. ABT-737, a BH3-only mimetic, targets the prosurvival Bcl-2 family and also induces apoptosis. GSI XX or ABT-737 alone inhibited cell proliferation in a dose dependent manner and combination drug treatment showed a synergistic antitumor effect in Notch expressing NSCLC in vitro. In vivo, this drug combination significantly suppressed tumor proliferation compared to single drug treatment. Phospho-Bcl-2 was down-regulated and Bax was up-regulated by both the single and combination drug treatments. Bim was induced by single drug treatment and was enhanced by combination treatment. Combination treatment-induced apoptosis was decreased by Bim inhibition, suggesting that the antitumor effect of the drug combination was dependent on Bim.
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