Efficient cancer therapy by regulating ceramide metabolism in cancer cells
Project/Area Number |
24590197
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Medical pharmacy
|
Research Institution | Nagasaki University |
Principal Investigator |
OZAKI Keiichi 長崎大学, 医歯薬学総合研究科(薬学系), 准教授 (50252466)
|
Project Period (FY) |
2012-04-01 – 2015-03-31
|
Project Status |
Completed (Fiscal Year 2014)
|
Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
|
Keywords | セラミド / 抗がん剤 / PI3 kinase / Akt / PI3キナーゼ / GCS / SPT / ビンクリスチン / ドキソルビシン / Ceramide / PI3-kinase |
Outline of Final Research Achievements |
Glucosylceramide synthase (GCS), which inactivates the apoptosis-inducing efficacy of ceramide, is highly expressed in cancer cell lines in which PI3 kinase/Akt pathway is constitutively activated. Specific blockade of activated PI3 kinase/Akt pathway decreased the mRNA expression and enzymatic activity of GCS in cancer cells, and then increased the sensitivity of cancer cells to doxorubicin and vincristine which are ceramide-inducing anti-tumor drugs. Moreover, suppression of GCS by a specific inhibitor or transfection of GCS siRNA also enhanced apoptosis inducing efficacy of doxorubicin and vincristine in cancer cells. These results suggest that GCS, a putative downstream effector of PI3 kinase/Akt pathway is a crucial molecular target for cancer treatment to determine the sensitivity of cancer cells to some anti-tumor drugs.
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Report
(4 results)
Research Products
(4 results)