2017 Fiscal Year Final Research Report
Elucidation of the resistant mechanism and the development of drugs for overcoming resistance against Cetuximab in head and neck cancer.
| Project/Area Number |
15H05039
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Surgical dentistry
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| Research Institution | Chiba University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
丹沢 秀樹 千葉大学, 大学院医学研究院, 教授 (50236775)
中嶋 大 千葉大学, 医学部附属病院, 助教 (50431747)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | セツキシマブ / 頭頚部癌 / 耐性 / PLAUR / Resveratrol |
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| Outline of Final Research Achievements |
Cetuximab is a recombinant human/mouse chimeric monoclonal antibody which competitively binds to epidermal growth factor receptor (EGFR) resulting in inhibition of cell growth, angiogenesis and invasion. Despite initial drug activity, some patients often have resistance against Cetuximab. The aim of this study is to discover the resistant mechanism and to detect a new drug, which overcomes the resistance. Microarray assay and real time PCR using 3 pairs of sensitive and resistant cells, which have been established by us, revealed that PLAUR gene may be a candidate resistant gene. Transformantion by PLAUR shRNA makes the resistant ability weaker. Via integrin β1 signal transduction pathway, overexpression of PLAUR gene upregulates cell growth resulting in acquire the resistance against Cetuximab. Resveratrol was detected as inhibitor of PLAUR gene and it was confirmed in vitro and in vivo that Resveratrol weakens the resistance against Cetuximab.
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| Free Research Field |
医歯薬学
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