Regulation of tumor growth mediated by pyruvate dehydrogenase PDH

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06815
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48040:Medical biochemistry-related
• Research Institution: Asahikawa Medical College
• Principal Investigator: Nakamaya Koh 旭川医科大学, 医学部, 教授 (10451923)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 腫瘍 / ピルビン酸脱水素酵素 / 代謝 / 遺伝子発現

Outline of Final Research Achievements

We aim to understand the role of energy metabolism during tumor development. First, we generated PDH knockout (KO) breast cancer cell line. These cells showed reduced cell proliferation. When these cells were inoculated into immunodeficient mice, tumor formation was significantly reduced. Next, we introduced an expression vector of PDH which can be induced by drug into these cells. When PDH expression was induced in PDH KO cells, tumor formation was recovered. Furthermore, when PDH was induced three weeks after cell inoculation, recovery of tumor formation was still observed. These results indicate that energy metabolism mediated by PDH plays an important role during later phase of tumor formation.

Free Research Field

腫瘍生化学

Academic Significance and Societal Importance of the Research Achievements

国内の乳がん患者数は年々増加しており、女性のがん罹患者の中で最も多い。本研究により、代謝酵素の一つPDHを乳がん細胞株でノックアウトすることにより、腫瘍形成が抑制されることが明らかになった。このことから、PDH抑制は乳がん増殖を阻害するための効果的なアプローチとなることが期待される。一方で、PDHは体内で幅広く発現しており、その活性を常時・全身性に抑制することは、さまざまな副作用を引き起こすことが予想される。本研究の成果は、PDHが腫瘍形成後期で重要な役割を担うことを示しており、PDH阻害薬を後期に限定して使用することで、副作用少なく、効果の高い乳がん治療法に結びつく展望が描かれた。