Construction of bases to develop senescence-senolysis induction therapy for oral squamous cell carcinoma

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K10092
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Osaka University
• Principal Investigator: Imai Tomoaki 大阪大学, 大学院歯学研究科, 招へい教員 (80599598)
• Co-Investigator(Kenkyū-buntansha): 森田 祥弘 大阪大学, 歯学部附属病院, 講師 (30590517)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 口腔癌 / 扁平上皮癌 / 動物モデル

Outline of Final Research Achievements

Senescence is a protective process against the development of cancer, when cells that are subjected to different stimuli stop growing permanently. Senescent cells trigger persistent inflammation in the surrounding area and display characteristics that encourage the development of cancer and the advancement of malignancy (known as SASP).
This study aimed to examine the molecular dynamics of senescence indicators and SASP components triggered by the anticancer drug, cisplatin (CDDP), in oral squamous cell carcinoma (OSCC) cell lines and animal experimental models.
CDDP treatment resulted in the observation of senescence with elevated p21 expression in tongue cancer mouse tissues and OSCC cell lines. The application of p21 inhibitors showed that p21-induced senescence stimulates the release of SASP factors.

Free Research Field

口腔外科学

Academic Significance and Societal Importance of the Research Achievements

口腔扁平上皮癌（OSCC）に対する薬物療法はシスプラチン（CDDP）が主体である。薬剤抵抗性に至ったOSCCによる細胞老化の分子生物学的な解明は、OSCCの悪性形質の分子機構の理解のみならず、臨床面においては切除不能な進行再発癌や多発性癌、転移性癌に対する抗腫瘍薬物療法の成績向上への新たな足掛かりになると考えられる。