The possiblity of resistance for anti-angiogenic therapy and therapeutic biomarker in tumor AMP-activated protein kinase

• Project/Area Number: 15K21555
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor therapeutics; Gastroenterology
• Research Institution: Kurume University
• Principal Investigator: Iwamoto Hideki 久留米大学, 医学部, 助教 (40529541)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 肝細胞癌 / 血管新生 / 血管新生抑制治療 / AMPK / 血管新生阻害剤 / エネルギー代謝 / 低酸素誘導因子 / 耐性 / ＡＭＰＫ

Outline of Final Research Achievements

The purpose of this study is to clarify whether energy metabolism is related to resistance for anti-angiogenic therapy. It is generally known that AMPK was activated when the cells falled into starved condition. We have found that AMPK was activated even in cancer cells by anti-angiogenic therapy. To know the function of tumor AMPK in anti-angiogenic therapy, we have generated AMPK deleted hepatoma cell lines. And we have performed in vitro and in vivo experiments using these cell lines. However, AMPK did not correlate with resistance for anti-angiogenic therapy. In contrast, inhibition of hypoxia inducible factor (HIF) showed significant anti-tumor effect for hepatocellular carcinoma.

Research Products

• [Journal Article] Antiangiogenic and Antitumor Actitivies of Aflibercept, a soluble VEGF receptor 1 and 2, in a mouse model of hepatocellular carcinoma (2016)
  • Author(s): Takuji Torimura, Hideki Iwamoto, Toru Nakamura, Mitsuhiko Abe, Yu Ikezono, Fumitaka Wada, Takahiko Sakaue, Hiroshi Masuda, Osamu Hashimoto, Hironori Koga, Takato Udeno, Hirohisa Yano
  • Journal Title: Neoplasia Volume: Vol18 No7 Pages: 413-424
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Inhibition of hypoxia-inducible factor via upregulation of von Hippel-Lindau protein induces "angiogenic switch off" in a hepatoma mouse model (2015)
  • Author(s): Hideki Iwamoto et al.
  • Journal Title: Molecular Therapy- Oncolytics Volume: 2 Pages: 15020-15020
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] PlGF-induced VEGFR1-dependent vascular remodeling determines opposing antitumor effect and drug resistance (2016)
  • Author(s): 岩本英希
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-10-06
• [Presentation] マウス肝癌モデルを用いたNotch抑制剤の効果検討 (2016)
  • Author(s): 岩本英希
  • Organizer: 第５２回肝臓学会総会
  • Place of Presentation: 千葉県 千葉市美浜区
  • Year and Date: 2016-05-19
• [Presentation] 腫瘍Transglutaminase2を標的とした新規血管新生阻害剤SQAPの肝細胞癌に対する効果の基礎的検討 (2015)
  • Author(s): 岩本英希
  • Organizer: 日本消化器病週間 肝臓大会
  • Place of Presentation: 東京都 グランドプリンス新高輪
  • Year and Date: 2015-10-08
• [Presentation] 肝癌における血管新生の重要性 (2015)
  • Author(s): 岩本英希
  • Organizer: 日本臨床分子形態学会
  • Place of Presentation: 長崎県 長崎大学医学部 ポンぺ会館
  • Year and Date: 2015-09-18