| Project/Area Number |
15K15002
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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 |
Medical pharmacy
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
中川 貴之 京都大学, 医学研究科, 准教授 (30303845)
今井 哲司 京都大学, 医学研究科, 講師 (80468579)
大村 友博 京都大学, 医学研究科, 助教 (00439035)
中川 俊作 京都大学, 医学研究科, 特定職員 (50721916)
金子 周司 京都大学, 薬学研究科, 教授 (60177516)
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 抗がん剤副作用 / 手足症候群 / 分子標的薬 / ヒト皮膚ケラチノサイト / マウスモデル |
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| Outline of Final Research Achievements |
The present study is designed to investigate mechanisms underlying epidermal growth factor receptor inhibitors (EGFRIs)- or multikinase inhibitors (MKIs)-induced Hand-Foot Syndrome (HFS) using a human keratinocyte cell line, HaCaT cell. We evaluated the effects of EGFRIs (gefitinib and erlotinib) or MKIs (sunitinib and sorafenib) on the viability of HaCaT cells using MTT assay. Each of the anti-cancer agents reduced the viability of Schwann cells in a concentration-dependent manner after either 24 or 48 h of treatment. The treatment with gefitinib and erlotinib significantly increased the expression of apoptosis marker caspase3, and reduced phospholylated Akt (p-Akt) levels, which involves in cell survival, suggesting that EGFRIs might induce HFS via cell apoptosis mechanisms. In contrary, sunitinib and sorafenib failed to affect caspase3 and p-Akt levels. These findings clearly suggest the different etiologic mechanisms underlying HFS depending on the classes of anti-cancer agents.
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