| Project/Area Number |
18K08689
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 55020:Digestive surgery-related
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
Ito Hiroshi 京都府立医科大学, 医学(系)研究科(研究院), 特任助教 (20732481)
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| Co-Investigator(Kenkyū-buntansha) |
大辻 英吾 京都府立医科大学, 医学(系)研究科(研究院), 教授 (20244600)
塩崎 敦 京都府立医科大学, 医学(系)研究科(研究院), 助教 (40568086)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 胃癌 / 胃十二指腸外科学 / 癌幹細胞 / イオンチャネル |
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| Outline of Final Research Achievements |
Cells strongly expressing CD44 were separated from MKN74 cells, a human gastric cancer cell line, using FACS, and cancer stem cells (CSCs) were identified based on tumorsphere formation. The gene expression profiles of CSCs were examined by microarray analysis, and the expression of several genes related to voltage-gated Ca2+ channels (VGCCs), including CACNA2D1 and CACNB4, were up-regulated. The CACNA2D1 inhibitor, Amlodipine, and the CACNB4 inhibitor, Verapamil, were more cytotoxic at a lower concentration in CSCs than in non-CSCs, and effectively decreased the number of tumorspheres. In a xenograft model in nude mice, the administration of Amlodipine or Verapamil with Cisplatin resulted in significantly smaller tumor volumes than those of Cisplatin alone. These results suggest that that VGCCs are involved in the maintenance of CSCs, and that their specific inhibitors, Amlodipine and Verapamil, have potential as a targeted therapeutic agent against gastric cancer.
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| Academic Significance and Societal Importance of the Research Achievements |
電位依存性カルシウムチャネルが胃癌幹細胞において高発現し、その阻害剤であるアムロジピンやベラパミルが癌幹細胞特異的に抑制効果を示すことを新たに見出した。アムロジピンは高血圧・狭心症治療薬として、ベラパミルは抗不整脈として臨床で広く用いられている薬剤であり、その抗腫瘍効果を明らかにしたことの社会的意義は大きいと考えられる。
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