| Project/Area Number |
11671426
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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 |
Orthopaedic surgery
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| Research Institution | kanazawa University |
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Principal Investigator |
TSUCHIYA Hiroyuki Kanazawa University School of Medicine Department of Orthopaedic, Associate Professor, 医学部, 助教授 (40227434)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1999: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Osteosarcoma / Gsplatin / Drug resistance / p53 gene / Caffeine / 骨肉腫 / シスプラチン / p53遺伝子 / カフェイン / 薬剤耐性 / p53 |
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| Research Abstract |
1) Alteration of p53 gene in human osteosarcoma cell lines : There was no overexpression of p53 gene and no point mutation from exon 5 to exon 8 in both OST cell line (sensitive to cisplatin) and OST-R cell line (resistant to cisplatin). It was considered that these two cell lines expressed wild-type p53 protein.
2) Analysis of p53 deletion in cisplatin-resistant human osteosarcoma cell (OST-R) : Deletion of p53 gene was significantly increased in OST-R cells. As the amount of p53 protein was decreased corresponding with this deletion, the function of p53 was suppressed and the instability of chromosome 17 was increased in OST-R.Perhaps, the function loss of p53 gene and protein would be an indicator of acquired cisplatin resistance in human osteosarcoma.
3) Alteration of p53 gene expression after chemotherapy and growth inhibition by controlling p53 expression : Caffeine has DNA-repair inhibiting effect and suppress p53 overexpression. The cytocidal effect of cisplatin was increased by caffeine in OST cells, but not in OST-R.The expression of p53 protein was overexpressed after cisplatin treatment and caffeine suppressed this overexpression in OST cells. Caffeine could not overcome the acquired cisplatin-resistance in human osteosarcoma.
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