Development of new therapy targeting HSP27 in colorectal cancer

2013 Fiscal Year Final Research Report

• Project/Area Number: 23591970
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Keio University
• Principal Investigator: ISHII YOSHIYUKI 慶應義塾大学, 医学部, 講師 (30255468)
• Project Period (FY): 2011 – 2013
• Keywords: Heat shock protein 27 / Colorectal cancer / Biomarker / Drug sensitivity

Research Abstract

High levels of heat shock protein 27 (HSP27) expression in colon cancer cell lines were associated with low 5-fluorouracil (5-FU) sensitivity. The suppression of HSP27 expression promoted 5-FU sensitivity in colon cancer cell lines in vitro and in vivo. Furthermore, the inhibition of HSP27 phosphorylation by a selective inhibitor promotes 5-FU sensitivity in colorectal cancer cell lines. Similarly, CPT-11 and l-OHP sensitivities were also associated with the expression levels of HSP27. Anti-EGF-R antibody drugs promoted CPT-11 sensitivity by suppressing the expression and the phosphorylation of HSP27. In an adjuvant chemotherapy group who underwent curative resection of colorectal cancer, the cases with low expression of HSP27 had better rate of relapse free survival than those with high expression of HSP27.
In conclusion, HSP27 may be a biomarker for sensitivity of anti-cancer drugs and new treatment in colorectal cancer.

Research Products

• [Journal Article] Inhibition of heat shock protein 27 phosphorylation promotes sensitivity to 5-fluorouracil in colorectal cancer cells (2014)
  • Author(s): Matsunaga A, Ishii Y, Tsuruta M, Okabayashi K, Hasegawa H, Kitagawa Y.
  • Journal Title: Oncology Letters Volume: (in press)
  • Peer Reviewed
• [Journal Article] Suppression of heat shock protein 27 expression promotes 5-fluorouracil sensitivity in colon cancer cells in a xenograft model (2012)
  • Author(s): Hayashi R, Ishii Y, Ochiai H, Matsunaga A, Endo T, Hasegawa H, and Kitagawa Y.
  • Journal Title: Oncology Reports Volume: 28(4) Pages: 1269-1274
  • DOI: 10.3892/or.2012.1935
  • Peer Reviewed
• [Presentation] 大腸癌に対する分子標的治療薬(抗EGFR抗体薬)の効果におけるHeat Shock Protein 27の役割 (2013)
  • Author(s): 石田隆,石井良幸,長谷川博俊,遠藤高志,岡林剛史,瀬尾雄樹,菊池弘人,清島亮,北川雄光
  • Organizer: 第68回の本消化器外科学会総会
  • Place of Presentation: 宮崎
  • Year and Date: 2013-07-17
• [Presentation] 大腸癌におけるバイオマーカーおよび治療標的としてのHeat Shock Protein 27 (2012)
  • Author(s): 石井良幸,落合大樹,松永篤志,石田隆,遠藤高志,長谷川博俊,北川雄光
  • Organizer: 第67回日本消化器外科学会総会
  • Place of Presentation: 富山
  • Year and Date: 2012-07-20
• [Presentation] 大腸癌における5-fluorouracil感受性の規定因子としてのHeat shock protein 27について, Heat shock protein 27 as a regulator of 5-fluorouracil sensitivity in colorectal cancer cells (2011)
  • Author(s): 松永篤志,石井良幸,長谷川博俊,遠藤高志,落合大樹,星野大樹,星野好則,茂田浩平,瀬尾雄樹,星野剛,北川雄光
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-05