2019 Fiscal Year Final Research Report

Senescence-associated secretory phenotype is involved in cisplatin-resistant of oral cancer

Research Project

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Project/Area Number	17K11843
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Surgical dentistry
Research Institution	Kochi University
Principal Investigator	SASABE Eri 高知大学, 教育研究部医療学系臨床医学部門, 講師 (40363288)
Co-Investigator(Kenkyū-buntansha)	山本哲也高知大学, 教育研究部医療学系臨床医学部門, 教授 (00200824) 仙頭慎哉高知大学, 教育研究部医療学系臨床医学部門, 助教 (30635264) 北村直也高知大学, 教育研究部医療学系臨床医学部門, 講師 (70351921)
Project Period (FY)	2017-04-01 – 2020-03-31
Keywords	細胞老化 / 口腔扁平上皮癌 / SASP
Outline of Final Research Achievements	Several chemotherapeutic drugs bring advanced complications including cancer resistance by the induction of senescence-associated secretory phenotype (SASP) to cancer cells. However, the involvement of SASP in the chemotherapeutic efficacy in oral squamous cell carcinoma (OSCC) cells is poorly understood. In this study, we investigated the involvement of SASP in the susceptibility of OSCC cells to cisplatin. A cisplatin-resistant strain (SAS/CR2 cells) was established by continued exposure of OSCC cells, SAS cells, to low concentrations of cisplatin. As compared with the parent strain, the proliferative ability of SAS/CR2 cells was reduced. In SAS/CR2 cells, the ratio of SA-β-gal positive cells and the expression of p21 and p53 were increased. Furthermore, the levels of SASP factors in culture supernatants were higher than those of control cells. These results suggest that SASP may be involved in cisplatin-resistant of OSCC cells.
Free Research Field	口腔外科
Academic Significance and Societal Importance of the Research Achievements	口腔癌は抗がん剤治療により一旦腫瘍の縮小が認められても、その後、がん細胞が抗がん剤に対する耐性を獲得することで腫瘍の再増殖が生じることが多い。本研究では、口腔がん細胞の抗がん剤耐性獲得における細胞老化の関与について検討し、多くの耐性細胞は細胞老化状態に陥っており、いくつかのサイトカインやケモカイン、エクソソームといった因子の分泌を介して周囲の細胞にも抗がん剤耐性を誘導することが明らかとなった。このことから、将来的には、細胞老化制御薬やSASP因子を標的とした分子標的治療薬などを現行の抗がん剤治療に併用することで、口腔癌の抗がん剤治療効果を向上できる可能性が示唆された。