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2022 Fiscal Year Final Research Report

Study on combined radiotherapy by inhibiting hyaluronic acid for radioresistant oral cancer

Research Project

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Project/Area Number 19K08141
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52040:Radiological sciences-related
Research InstitutionHirosaki University

Principal Investigator

Hosokawa Yoichiro  弘前大学, 保健学研究科, 教授 (70173599)

Project Period (FY) 2019-04-01 – 2023-03-31
Keywordsヒアルロン酸 / 放射線治療 / 放射線抵抗性 / 癌幹細胞
Outline of Final Research Achievements

As an attempt to eradicate radioresistant cells generated during radiotherapy, we investigated the effect of 4-methylumbelliferone (4-MU), a hyaluronan synthesis inhibitor, in combination with radiation. As a result, 4-MU administration suppressed cell survival rate and cell migration, suppressed cancer stem cell-like phenotype, and enhanced oxidative stress. When HAS3, which was highly expressed in radioresistant cells, was targeted and knocked down by siRNA, suppression of cell viability and enhancement of radiosensitization effect were observed. These results suggest that HAS3 is an important factor in radiation resistance, and that direct inhibition of HAS3 or inhibition of hyaluronic acid synthesis may enhance the radiosensitizing effect.

Free Research Field

放射線腫瘍学

Academic Significance and Societal Importance of the Research Achievements

放射線治療は、近年の高精度照射技術の発展によって治療適応が拡大し、癌治療において重要な位置を占めている。しかし標準的放射線治療では癌細胞集団の一部が放射線抵抗性を獲得し、再発や遠隔転移を引き起こすことが問題視されている。放射線抵抗性細胞に有効な薬剤や治療戦略は未だ確立されていないため、放射線治療の予後改善のためにこの課題解決は急務である。ヒアルロン酸合成阻害剤として知られている4-メチルウンベリフェロンは、様々な癌細胞で抗腫瘍/転移効果を示すことが報告されている。そこで本研究では、放射線抵抗性腫瘍細胞株を使用し、4-メチルウンベリフェロンと放射線との併用効果を研究した。

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Published: 2024-01-30  

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