2007 Fiscal Year Final Research Report Summary
Screening and validation of target molecules involved in mechanism of multi-modality therapy
| Project/Area Number |
18590838
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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 |
Respiratory organ internal medicine
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| Research Institution | Chiba University |
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Principal Investigator |
TAKIGUCHI Yuichi Chiba University, Chiba University Hospital, Dept Respirol, Associate Professor (30272321)
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| Co-Investigator(Kenkyū-buntansha) |
KUROSU Kstsushi Chiba University, Graduate School, Dept Respirol, Assistant Prof (20291106)
KASAHARA Yasunori Chiba University, Graduate School, Dept Respirol, Assistant Prof (60343092)
SEKI Naohiko Chiba University, Graduate School, Dept Genome Sci, Assoc Prof (50345013)
HIROSHIMA Kenzo Chiba University, Graduate School, Dept Pathol, Assoc Prof (80218833)
KURIYAMA Takayuki Chiba University, Graduate School, Dept Respirol, Professor (20009723)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Cisplatin / Gene expression / cDNA microarray / siRNA / Radiotherapy / Multi-modality therapy / Cell cycle |
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| Research Abstract |
Background: Substantial evidence has disclosed that some cytotoxic agents have complex activities in influencing signal transduction pathways in cells. Materials and Methods: cDNA microarray analysis was performed after exposing a human squamous cell carcinoma cell line, RERF-LC-AI, to low-dose cisplatin for 5 days. Up-regulated gene expressions were suppressed by small interfering RNA to investigate phenotypic alteration of the cells. Results: Among 30,000 genes screened, 42 genes showed increases or decreases in expression of more than 2-fold in cisplatin treatment. They included genes with functions involved in apoptosis, cell cycle regulation and DNA metabolism/repair. Suppression of the most significantly altered 5 genes by small interfering RNA resulted in partly reduced apoptosis without altering cytotoxicity of cisplatin. Conclusion: Besides direct cytotoxic effects on cells, cisplatin may have indirect effects involving drug resistance, and synergistic effects with other agents.
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