| Project/Area Number |
17591423
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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 |
Digestive surgery
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| Research Institution | Fukushima Medical University |
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Principal Investigator |
TERASHIMA Masanori Fukushima Medical University, School of Medicine, Department of Surgery, Associate Professor, 医学部, 助教授 (40197794)
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| Co-Investigator(Kenkyū-buntansha) |
GOTOH Mitsukazu Fukushima Medical University, School of Medicine, Department of Surgery, Professor, 医学部, 教授 (50162160)
KOGURE Michihiko Fukushima Medical University, School of Medicine, Deportment of Surgery, Assistant Professor, 医学部, 講師 (90264548)
HOSHINO Yutaka Fukushima Medical University, School of Medicine, Deportment of Surgery, Instructor, 医学部, 助手 (30295414)
樫村 省吾 福島県立医科大学, 医学部, 助手 (80398346)
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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 |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Methylation / 5-fluorouracil / thymidylate synthase / 5-aza-deoxy citidine / 5-aza-2'-deoxycitidine |
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| Research Abstract |
We investigated the changes in drug sensitivity against 5-fluorouracil by adding 5-aza-2'-deoxycitidine (5-aza) (2 μM) in a total of 7 gastrointestinal cancer cell lines (MKN-1, MKN-45, MKN-74, C-1, Panc-1, MIaPaCa-2, HuH-7) using MTT assay and found that sensitivity to 5-FU significantly decreased in MKN-1, MKN-74, Panc-1, MIaPaCa-2. We also investigated the changes in 5-FU metabolism associated enzyme gene (thymidylate synthase (TS), dihydropyrimidine dehydroohgenase (DPD), orotatephosphoribosyl transferase (OPRT), thymidine phospholyrsase (TP), ribonucleotide reductase (RNR)) by adding 2 μM or 10μM of 5-aza using real-time RT-PCR. The expression levels were upregulated by 5-aza in a dose dependent manner in most of genes except for DPD. From these results, it is suggested that 5-FU metabolism associated enzyme gene are highly methylated in human gastrointestinal cancer cell lines. We further investigated the correlation between the changes in gene expression level and drug sensitivity. It is found that up-regulation of TS significantly correlated with the decreased drug sensitivity.
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