| Project/Area Number |
17590610
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Akita University |
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Principal Investigator |
OTAKA Michiro Akita University, school of medicine, Assistant professor, 医学部, 講師 (30250872)
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| Co-Investigator(Kenkyū-buntansha) |
WATANABE Sumio Jyuntendo University, schoolof medicine, Professor, 医学部, 教授 (20138225)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2005: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | MEK-ERK signaling / anti-apoptosis / COX-2 / 薬剤代謝関連遺伝子 |
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| Research Abstract |
For the study, caMEK expressing IEC-6 rat intestinal epithelial cells (IEC-caMEK cells) were generated. Cells were treated with various concentrations of CPT-11, and the inhibitory concentration of 50% (IC_<50>) was determined by WST assay. Apoptosis was evaluated with DNA staining and quantitative analysis of fragmented DNA. Protein expressions were determined by western blot analysis. We also examined the role of cyclooxygenase-2 (COX-2) in CPT-11 induced apoptosis in the cell systems. IEC-caMEK cells possessed survival advantages following serum starvation, or following treatment with CPT-11 compared to empty vector transfected cells. In the conditions, apoptosis was remarkably suppressed in IEC-caMEK cells. Western blot analysis revealed that increased expression of Bcl-2, Bcl-xL, Mcl-1, COX-2, and decreased expression of Bak in IEC-caMEK cells. The COX-2 selective inhibitor, NS398, ameliorated antiapoptotic nature of IEC-caMEK cells in the CPT-11-induced apoptosis. MEK activation led to suppress CPT-11-induced apoptosis in normal intestinal epithelial cells via COX-2-dependent mechanism. Therefore, the MEK-ERK signaling may contribute to drug resistant nature of cancer cells. COX-2 may also play an important role in this process.
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