Potent in vitro and in vivo antitumor effects of MDM2 inhibitor nutlin-3 in gastric cancer cells

• Project/Area Number: 22590497
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied pharmacology
• Research Institution: University of Tsukuba
• Principal Investigator: HYODO Ichinosuke 筑波大学, 医学医療系, 教授 (60416469)
• Co-Investigator(Kenkyū-buntansha): ABEI Masato 筑波大学, 医学医療系, 准教授 (20261802) ; SUZUKI Hideo 筑波大学, 医学医療系, 准教授 (00400672)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 胃癌 / MDM2 / p53 / siRNA / SIRT1

Research Abstract

Murine double minute 2 (MDM2) is a negative regulator of p53. An MDM2 inhibitor, nutlin-3, stabilized p53 and induced apoptosis in the gastric cell lines with wild-type p53. An in vivo antitumor effect of nutlin-3 alone and its additiveaugmentation by 5-fluorouracil were confirmed in MKN-45 xenograft tumor model. Nutlin-3 showed potent antitumor activity against human gastric cancer cells with wild-type p53 and shows promise as a single agent and in combination with conventional anticancer drugs.

Research Products

• [Journal Article] Potent in vitroand in vivo anti-tumor effects of MDM2 inhibitor nutlin-3 in gastric cancer cells (2011)
  • Author(s): Endo S, Yamato K, Hirai S, MoriwakiT, Fukuda K, Suzuki H, Abei M, Nakagawa I, Hyodo I.
  • Journal Title: Cancer Sci Volume: 102(3) Pages: 605-13
  • Peer Reviewed
• [Journal Article] Potent in vitro and in vivo antitumor effects of MDM2 inhibitor nutlin-3 in gastric cancer cells (2011)
  • Author(s): Shinji Endo
  • Journal Title: Cancer Science Volume: 102 Issue: 3 Pages: 605-613
  • DOI: 10.1111/j.1349-7006.2010.01821.x
  • Peer Reviewed
• [Journal Article] Potent in vitro and in vivo antitumor effects of MDM2 inhibitor nutlin-3 in gastric cancer cells. (2011)
  • Author(s): Endo S, Hyodo I, et al.
  • Journal Title: Cancer Science Volume: 102 Pages: 605-613
  • NAID: 10029291334
  • Peer Reviewed
• [Presentation] 胃癌におけるMDM2及びp53蛋白発現の免疫組織学的検討 (2012)
  • Author(s): 兵頭 一之介
  • Organizer: 日本消化器病学会
  • Place of Presentation: 神戸国際会議場（神戸市）
• [Presentation] ヒト胃癌細胞株におけるMDM2阻害剤nutlin-3の抗腫瘍効果について (2010)
  • Author(s): 遠藤慎治,鈴木英雄,平井祥子,兵頭一之介,大和建嗣
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場,大阪市
  • Year and Date: 2010-09-22
• [Presentation] The anti-tumor effect of MDM2 antagonist nutlin-3 in gastric cancer cell in vitro and in vivo (2010)
  • Author(s): Endo S, Suzuki H, Hirai S, Hyodo I, Yamato K
  • Organizer: 第101回米国癌学会第101回米国癌学会
  • Place of Presentation: ワシントン,米国
  • Year and Date: 2010-04-20