2014 Fiscal Year Final Research Report
Analysis of a novel small-molecule compound inducing the degradation of a cisplatin resistance-related factor ERCC1
| Project/Area Number |
25640089
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Tumor therapeutics
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
INOBE Manabu 金沢大学, 薬学系, 准教授 (10312414)
WAKASUGI Mitsuo 金沢大学, 薬学系, 助教 (80345595)
NISHINAGA Mari 富山県衛生研究所, 研究員 (10646681)
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| Co-Investigator(Renkei-kenkyūsha) |
KUNISHIMA Munetaka 金沢大学, 薬学系, 教授 (10214975)
ODA Akifumi 金沢大学, 薬学系, 准教授 (50433511)
ENDO Yoshio 金沢大学, がん進展制御研究所, 准教授 (30211783)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Keywords | ヌクレオチド除去修復 / 阻害剤 / 抗癌剤 / シスプラチン / 低分子化合物 / 増感作用 |
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| Outline of Final Research Achievements |
In this study, we have analyzed whether a small-molecule inhibitor of nucleotide excision repair (NERi) we recently found can potentiate the cytotoxic effects of cisplatin in cancer cells. The clonogenic survival assay revealed that NERi treatment increases the cisplatin-sensitivity of KKLS stomach cancer cell lines and A2780 ovarian cancer cell lines 2-3 fold. Using an immunoassay with damage-specific antibody, we showed that the removal of cisplatin-induced DNA intrastrand crosslinks is markedly attenuated by NERi treatment. Furthermore, in vivo experiments using murine Lewis lung carcinoma and C57BL/6 mice revealed that a combination of cisplatin and NERi significantly suppresses tumor growth, compared with cisplatin alone.
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| Free Research Field |
分子細胞生物学
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