2003 Fiscal Year Final Research Report Summary
Basic Research of Novel Molecular Target on Cancer Chemotherapy
| Project/Area Number |
14570122
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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 |
Pathological medical chemistry
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| Research Institution | Nagasaki University |
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Principal Investigator |
GOTO Shinji Nagasaki University, Graduate School of Biomedical Sciences, Research Associate, 大学院・医歯薬学総合研究科, 助手 (50186889)
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| Co-Investigator(Kenkyū-buntansha) |
KONDO Takahito Nagasaki University, Graduate School of Biomedical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (00158908)
IHARA Yoshito Nagasaki University, Graduate School of Biomedical Sciences, Associate Professor, 大学院・医歯薬学総合研究科, 助教授 (70263241)
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| Project Period (FY) |
2002 – 2003
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| Keywords | glutathione S-transferasen / drug resistance / nuclear translocation / cisplatin / doxorubicin / cancer |
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| Research Abstract |
Recent study has shown that nuclear glutathione S-transferase (GST)n accumulates in cancer cells resistant to doxorubicin hydrochloride (DOX) and may function to prevent nuclear DNA damage caused by DOX (Goto et al., FASEB J., 15, 2702-2714 (2001)). It is not clear if the amount of nuclear GSTn increases in response to other anti-cancer drugs and if so, what is the physiological significance of the nuclear transfer of GSTt in the acquisition of drug-resistance in cancer cells. In the 'present study, we employed three cancer cell lines, HCT8 human colonic cancer cells, A549 human lung adenocarcinoma cells, and T98G human glioblastoma cells. We. estimated the nuclear transfer of GSTn induced by the anti-cancer drugs cisplatin (CDDP), irinotecan hydrochloride (CPT 11), etoposide (VP-16) and 5-fluorouracil (5-FU). It was found that : (1) Nuclear GSTn accumulated in these cancer cells in response to CDDP, DOX, CPT 11, VP-16 and 5-FU. (2) An inhibitor of the nuclear transport of GSTn, edible mushroom lectin (Agaricus bisporus lectin, ABL), increased the sensitivity of the cancer cells to DOX and CDDP, and partially to CPT 11. Treatment with ABL had no apparent effect on the cytotoxicity of VP-16 and 5-FU. These results suggest that inhibitors of the nuclear transfer of GSTn have practical value in producing an increase of sensitivity to DOX, CDDP and CPT 11.
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Research Products
(2 results)
