Elucidation of the radioresistance mechanism via Nrf2 antioxidant pathway in oral squamous cell carcinoma controlled by cancer metabolism

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K17145
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Kumamoto University
• Principal Investigator: Matsuoka Yuichiro 熊本大学, 大学院生命科学研究部(医), 特定研究員 (10802100)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 口腔癌 / 放射線耐性 / Nrf2 / がん糖代謝

Outline of Final Research Achievements

Our research aimed to elucidate the biological effects of tNrf2 anti-oxidant pathway on radioresistance in oral squamous cell carcinoma (OSCC) and Nrf2-dependent radioresistance mechanism in cancer glucose metabolism. Nrf2 was upregulated in clinical radioresistant cells in in vitro and in vivo experiments, and increased Nrf2 expression was associated with radioresistance. In addition, Nrf2-dependent glycolysis was involved in the development of radioresistance. Furthermore, phosphorylated Nrf2 expression was associated with histopathological response to chemoradiotherapy, and its expression correlated with poor prognosis in patients with advanced OSCC. These results suggested that Nrf2 plays an important role in OSCC radioresistance accompanied with metabolic modulation.

Free Research Field

口腔がん

Academic Significance and Societal Importance of the Research Achievements

継続的放射線照射によって耐性を獲得した臨床的放射線耐性細胞（CRR細胞）は、標準的な放射線治療線量である2GyのX線を毎日照射しても安定して生存し続けることから、放射線耐性機序を解析するための臨床的なモデルがん細胞として非常に有用な資材であり、学術的独自性が高いと考えられる。そのため、CRR細胞を用いて放射線耐性におけるNrf2依存的な代謝経路を解析し、Nrf2の代謝調節を標的とした放射線抵抗性口腔扁平上皮癌に対する治療戦略は新規治療の開発の観点で意義が深い。