Suppression of angiogenesis and metastasis on OSCC using epigenetical agents.

• Project/Area Number: 19791482
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Surgical dentistry
• Research Institution: Tohoku University
• Principal Investigator: SHINOHARA Fumiaki Tohoku University, 病院, 助教 (80400258)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,600,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥300,000); Fiscal Year 2008: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2007: ¥2,300,000 (Direct Cost: ¥2,300,000)
• Keywords: 口腔外科学一般(含病態検査学) / 血管新生 / 口腔癌 / VEGF / エピジェネティクス

Research Abstract

本研究では各種癌細胞株を用いて、エピジェネティクス制御剤(SAHA、ZEB)と各種抗癌剤(5-Fu、CDDP)を併用し、抗腫瘍効果と、血管新生因子の産生について解析した。抗癌剤単独処理に比較し、エピジェネティクス制御剤を併用することで、アポトーシスが増強する一方で、血管新生因子(VEGF-A, VEGF-C)の産生を抑制した。この抑制メカニズムとして、ZEBによるHIF-1aの分解と、また、エピジェネティクス制御剤によるVEGFの抑制が、抗癌剤誘導性のアポトーシス増強に直接関与しているわけではないことが示唆された。エピジェネティクス制御剤は口腔癌の薬剤感受性増強や癌の血管新生抑制に有効であることが示唆された。しかし、エピジェネティクス制御剤の効果は、併用する抗癌剤の種類、細胞種により異なり、抗癌剤の代謝や抗腫瘍効果の作用機序に依存していることが推察され、臨床応用に向けて、更なる解析が必要である。

Research Products

• [Journal Article] Enhancement of cisplatin cytotoxicity by SAHA involves endoplasmic reticulum stress-mediated apoptosis in oral squamous cell carcinoma cells (2009)
  • Author(s): Suzuki M, Endo M, Shinohara F, Echigo S and Rikiishi H.
  • Journal Title: Cancer Chemo. Pharma. (Online Pub)
  • Peer Reviewed
• [Journal Article] Zebularine suppresses the apoptotic potential of 5-Fuorouracil via cAMP/PKA/CREB pathway against human oral squamous cell carcinoma cells (2009)
  • Author(s): Maiko Suzuki
  • Journal Title: Cancer Chemotherapy and Pharmacology (印刷中)
  • Peer Reviewed
• [Journal Article] Zebularine suppresses the apoptotic potential of 5-fluorouracil via cAMP/PKA/CREB pathway against human oral squamous cell carcinoma cells (2008)
  • Author(s): Suzuki M, Shinohara F, Endo M, Sugazaki M, Echigo S and Rikiishi H.
  • Journal Title: Cancer Chemo. Pharma. (Online Pub)
  • Peer Reviewed
• [Journal Article] Zebularine-induced reduction in VEGF secretion by HIF-1α degradation in oral squamous cell carcinoma (2008)
  • Author(s): Suzuki M, Shinohara F and Rikiishi H.
  • Journal Title: Mole. Med. Repo. (1) Pages: 465-471
  • Peer Reviewed
• [Journal Article] Zebularine-induced reduction in VRGF secretion by HIF-α degradation in oral squamous cell carcinoma (2008)
  • Author(s): Maiko Suzuki
  • Journal Title: Molecular Medicine Reports 1 Pages: 465-471
  • Peer Reviewed
• [Journal Article] Zebularine induced a reduction in VEGF secretion by HIF-la degradation in oral squamous cell carcinoma (2008)
  • Author(s): Maiko Suzuki
  • Journal Title: Molecular Medicine Reports (In press)
  • Peer Reviewed
• [Journal Article] Epigenetic regulation of chemosensitivity to 5-fluorouracil and cisplatin by zebularine in oral squamous cell carcinoma (2007)
  • Author(s): Suzuki M, Shinohara F, Nishimura K, Echigo S and Rikiishi H.
  • Journal Title: Int. J. Oncology (31) Pages: 1449-1456
  • Peer Reviewed
• [Journal Article] Epigeneteic regulation of susceptibility to anti-cancer drugs in HSC-3 cells (2007)
  • Author(s): Suzuki M, Shinohara F, Nishimura K, Sato Y, Echigo S and Rikiishi H.
  • Journal Title: Interface Oral Health Science Pages: 279-280
  • Peer Reviewed
• [Journal Article] Chemosensitization of oral squamous cell carcinoma cells to cisplatin by histone deacetylase inhibitor, Suberoylanilide hydroxamic acid. (2007)
  • Author(s): Rikiishi H, Shinohara F, Sato T, Sato Y, Suzuki M and Echigo S.
  • Journal Title: Int. J. Oncology (30) Pages: 1181-1188
  • Peer Reviewed
• [Journal Article] Chemosensitization of oral squamous cell carcinoma cells to cisplatin by histone deacetylase inhibitor, suberoylanilide hydroxamic acid. (2007)
  • Author(s): Hidemi Rikiishi
  • Journal Title: INTERNATIONAL JOURNAL OF ONCOLOGY 30 Pages: 1181-1188
  • Peer Reviewed
• [Journal Article] Epigenetic regulation of chemosensitivity to 5-fluorouracil and cisplatin by zebularine in oral squamous cell carcinoma. (2007)
  • Author(s): Maiko Suzuki
  • Journal Title: INTERNATIONAL JOURNAL OF ONCOLOGY 31 Pages: 1449-1456
  • Peer Reviewed
• [Presentation] Effects of Zebularine on the apoptosis of 5-Fluorouracil via cAMP/PKA/CREB pathway against human oral squamous cell carcinoma cells (2009)
  • Author(s): Maiko Suzuki, Fumiaki Shinohara, Manabu Endo, Masaki Sugazaki, Seishi Echigo and Hidemi Rikiishi.
  • Organizer: The 3rd International Symposium for interface Oral Health Science
  • Year and Date: 2009-03-15
• [Presentation] エピジェネティクス制御剤を用いた癌血管新生の抑制 (2008)
  • Author(s): 鈴木麻衣子、篠原文明、遠藤学、力石秀実
  • Organizer: 第38回免疫学会総会
  • Year and Date: 2008-12-01
• [Presentation] 口腔癌の血管新生とエピジェネティクス制御 (2008)
  • Author(s): 鈴木麻衣子
  • Organizer: 歯科基礎医学会学術大会
  • Place of Presentation: 東京
  • Year and Date: 2008-09-24
• [Presentation] Zebularineによる抗癌剤感受性のエピジェネティクス制御 (2007)
  • Author(s): 鈴木麻衣子、篠原文明、西村謙太郎、力石秀実
  • Organizer: 第37回免疫学会総会
  • Year and Date: 2007-11-22
• [Presentation] エピジェネティクス制御化合物と抗癌剤の併用による口腔癌のアポトーシス誘導効果 (2007)
  • Author(s): Maiko Suzuki
  • Organizer: 第49回 歯科基礎医学会学術大会・総会
  • Place of Presentation: 札幌