Efficient cancer therapy by regulating ceramide metabolism in cancer cells

2014 Fiscal Year Final Research Report

• 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
• Keywords: セラミド / 抗がん剤 / PI3 kinase / Akt

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.

Free Research Field

生化学 分子生物学