Investigation of SIRT1-function and the effect of SIRT1 inhibitor in endometrial cancer

• Project/Area Number: 15K10711
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Shinshu University
• Principal Investigator: Asaka Ryoichi 信州大学, 学術研究院医学系(医学部附属病院), 助教 (00623688)
• Co-Investigator(Kenkyū-buntansha): 塩沢 丹里 信州大学, 学術研究院医学系, 教授 (20235493) ; 宮本 強 信州大学, 学術研究院医学系, 准教授 (70418721)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: SIRT1 / サーチュイン / 子宮内膜癌 / 卵巣癌 / 抗がん剤耐性 / 癌幹細胞 / SIRT1阻害薬 / Sirtuin1 / 酸化ストレス耐性 / シスプラチン

Outline of Final Research Achievements

SIRT1 expression was enhanced in ovarian cancer tissues and the patients with strong expression of SIRT1 showed a poor prognosis. Cytotoxic stress caused by anticancer drugs and hydrogen peroxide enhanced the SIRT1 expression, suppression of SIRT1 expression attenuated the resistance against anticancer agents and forced-expression of SIRT1 enhanced that. Thus, SIRT1 may enhance the cell viability against cytotoxic stress such as anticancer drugs. SIRT1 promoted anchorage-independent colonization in soft agar and enhanced the expression of stemness-related genes such as Nanog. Thus, SIRT1 may act on stem cell maintenance and this function may also be involved in enhancing cell viability by SIRT1. The SIRT1 inhibitor, EX527, canceled the anchorage-independent colonization promoted by SIRT1 and enhanced the antitumor effect of cisplatin.

Research Products

• [Journal Article] SIRT1 Regulates the Chemoresistance and Invasiveness of Ovarian Carcinoma Cells (2017)
  • Author(s): Mvunta David Hamisi、Miyamoto Tsutomu、Asaka Ryoichi、Yamada Yasushi、Ando Hirofumi、Higuchi Shotaro、Ida Koichi、Kashima Hiroyasu、Shiozawa Tanri
  • Journal Title: Translational Oncology Volume: 10 Issue: 4 Pages: 621-631
  • DOI: 10.1016/j.tranon.2017.05.005
  • Peer Reviewed / Open Access
• [Journal Article] Elevated Serum Levels of Estradiol Induce Endometrial Hyperplasia Rather than Carcinoma in a Mouse Model Using a Carcinogen (2017)
  • Author(s): Asaka Ryoichi、Miyamoto Tsutomu、Yamada Yasushi、Ando Hirofumi、Mvunta David Hamisi、Kobara Hisanori、Kashima Hiroyasu、Shiozawa Tanri
  • Journal Title: Journal of Carcinogenesis & Mutagenesis Volume: 08 Issue: 06 Pages: 1-6
  • DOI: 10.4172/2157-2518.1000308
  • Peer Reviewed / Open Access
• [Journal Article] Overexpression of SIRT1 is Associated With Poor Outcomes in Patients With Ovarian Carcinoma. (2016)
  • Author(s): Mvunta DH, Miyamoto T, Asaka R, Yamada Y, Ando H, Higuchi S, Ida K, Kashima H, Shiozawa T.
  • Journal Title: Applied Immunohistchemistry ＆ Molecular Morphology Volume: - Issue: 6 Pages: 415-421
  • DOI: 10.1097/pai.0000000000000316
  • Peer Reviewed / Open Access
• [Journal Article] Sirtuin 1 promotes the growth and cisplatin resistance of endometrial carcinoma cells: a novel therapeutic target. (2015)
  • Author(s): Asaka R, Miyamoto T, Yamada Y, Ando H, Mvunta DH, Kobara H, Shiozawa T
  • Journal Title: Lab Invest Volume: 95 Issue: 12 Pages: 1363-73
  • DOI: 10.1038/labinvest.2015.119
  • Peer Reviewed / Open Access