2014 Fiscal Year Final Research Report
Combined antitumor effec ot g-secretase inbitiro and ABT-737
| Project/Area Number |
24591146
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Hokkaido University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
KINOSHITA Ichiro 北海道大学, 大学院医学研究科, 准教授 (40343008)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Keywords | 併用治療効果 / 肺癌 / Notch |
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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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| Free Research Field |
呼吸器腫瘍
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