| Project/Area Number |
23501316
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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 |
Clinical oncology
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| Research Institution | Kinki University |
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Principal Investigator |
OKAMOTO Kunio 近畿大学, 医学部附属病院, 助教 (90460865)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAGAWA Kazuhiko 近畿大学, 医学部, 教授 (40298964)
OKAMOTO Isamu 九州大学, 医学部, 准教授 (10411597)
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| Project Period (FY) |
2011 – 2013
|
| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2013: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2012: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2011: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | 臨床腫瘍学 / 分子標的治療 / 腫瘍治療学 / EGFR / ゲフィニチブ / ゲフィチニブ |
|---|
| Research Abstract |
The molecular mechanism by which epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) induce apoptosis in non-small cell-lung cancer (NSCLC) cells that are positive for activating mutations of the EGFR remains unclear. In this study, we report the effects of the EGFR-TKI gefitinib on expression of the antiapoptotic protein survivin that have functional consequences in EGFR mutation-positive NSCLC cells. Immunoblot analysis revealed that gefitinib downregulated survivin expression, likely through inhibition of the PI3K-AKT signaling pathway, in NSCLC cells positive for EGFR mutation. Stable overexpression of survivin attenuated gefitinib-induced apoptosis and also inhibited the antitumor effect of gefitinib in human tumor xenografts. Our results indicate that downregulation of survivin plays a pivotal role in gefitinib-induced apoptosis in EGFR mutation-positive NSCLC cells.
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