2022 Fiscal Year Final Research Report
Expression and role of voltage-gated calcium channels in gastric cancer and cancer stem cells.
Project/Area Number |
20K09016
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 55020:Digestive surgery-related
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Research Institution | Kyoto Prefectural University of Medicine |
Principal Investigator |
Shiozaki Atsushi 京都府立医科大学, 医学(系)研究科(研究院), 講師 (40568086)
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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)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Keywords | 胃癌 |
Outline of Final Research Achievements |
Cells exhibiting strong CD44 activity were isolated from MKN74 gastric cancer (GC) cells by cell sorting, and cancer stem cells (CSCs) were generated with the sphere formation assay. Microarray analysis revealed CACNA2D1 was upregulated in CSCs, and its inhibitor amlodipine effectively decreased the number of tumorspheres. An immunohistochemical analysis revealed a relationship between strong CACNA2D1 expression and a poor prognosis in GC patients. CACNA2D1 was overexpressed in MKN7 and HGC27 cells, and CACNA2D1 depletion with siRNA suppressed cell proliferation, cell cycle progression, and invasion/migration, and induced apoptosis. The results of the microarray analysis showed that the apoptosis signaling pathway was enhanced via p53, BAX, and caspase 3 in CACNA2D1-depleted cells. These results provide an insight into the role of CACNA2D1 as a biomarker, and that its specific inhibitor, amlodipine, has potential as a targeted therapeutic agent against GC.
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Free Research Field |
消化器外科学
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Academic Significance and Societal Importance of the Research Achievements |
CACNA2D1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臨床で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。また、CACNA2D1のアポトーシスシグナル伝達経路を介する新たな腫瘍進展制御機構や、予後因子としての意義を明らかにし、バイオマーカーや治療標的としての可能性を示した。
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