| 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)
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| 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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