| Project/Area Number |
13671244
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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 |
General surgery
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| Research Institution | Kyushu University |
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Principal Investigator |
MIZUMOTO Kazuhiro Department of Surgery and Oncology, Graduate School of Medical Sciences, Assistant Professor, 医学部附属病院, 講師 (90253418)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Masao Department of Surgery and Oncology, Graduate School of Medical Sciences, Professor, 大学院・医学研究院, 教授 (30163570)
NAGAI Eishi Department of Surgery and Oncology, Graduate School of Medical Sciences, Assistant Professor, 医学部附属病院, 助手 (30264021)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2001: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | centrosome / mitotic catastrophe / centrosome overduplication / cell death / pancreatic cancer / 放射線照射 |
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| Research Abstract |
Anti-cancer chemotherapy constitutes the major approach of anti-cancer strategy. Such agents act by different mechanisms, but commit a similar cell death process on targeted cells. Centrosome overduplication could be documented as one event involving in radiation-induced cell death. In order to elucidate whether this centrosome abverrance is an unique outcome followed by nuclear DNA damage or a universal phenomenon in relation to cell apoptosis, in this study, we utilized a series of chemo-agents with different mechanism leading treated cells to apoptosis.
Human pancreatic cancer cell lines Suit-2 and Capan-2 were used in these experiments. Anti-cancer chemo-agents used in the study included etoposide (VP-16), mitomycin (MMC), cisplatin and 5-fluorouracil (5-FU). Centrosomes were visualized with indirect immunofluorescent microscopy after labeled by special anti-α-tubulin and anti-pericentrin. Cell apoptosis was evaluated by the micronucleus formation and cell death was determined by measuring fluorescence intensity of propidium iodide.
All used chemo-agents could cause some degree of centrosome abnormality in the two cell lines, even though distinct profile of the abnormality were present in different cells. VP-16-induced centrosome aberrance was apparently dose dependent. The continuous low dose VP-16 administration (1 μM) caused a marked multi-centrosome abnormality but only moderate cell death in Suit-2 cells. Same continuous treatment with 10 μM of VP-16 in turn resulted in high occurrence of micronuclei formation as well as that of multi-nuclear giant cell formation. We also observed more centrosome number abnormality within these giant cells.
The frequent visualizations of multinuclear giant cells and centrosome aberrance provide a strong impression of mitosis failure, which in turn could contribute to mitosis cell death. However, the novel concept of mitosis failure would undergo more intensive investigation.
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