The role of mTOR and HSP90 against oral cancer induced angiogenesis

• Project/Area Number: 23890124
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Surgical dentistry
• Research Institution: Okayama University
• Principal Investigator: OKUI Tatsuo 岡山大学, 岡山大学病院, 医員 (40610928)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: HSP90 / mTOR / 口腔癌 / 血管新生 / 癌血管新生

Research Abstract

From surgically resected lower gingival squamous cell carcinoma samples, CD31 and VEGFR2 were highly expressed in vascular endothelial cells, and VEGF-A was expressed in tumor cells. The combination treatment of HSP90 inhibitor and mTOR inhibitor significantly inhibited VEGF induced cell proliferation, tube formation of human umbilical vein endothelial cells (HUVEC) more than the single treatment of them. Gelatin zymography showed that the combination treatment inhibited the activation of MMP-2 induced by VEGF in HUVEC more than the single treatment of them. Immunohistochemical analysis of mice xenografted with SAS oral squamous cell carcinoma cells showed a significant reduction in CD31-positive tumor vasculature in HSP90 inhibitor and mTOR inhibitor-administrated mouse tumor sections compared with the single treatment of them. Furthermore, the combination treatment of them suppressed both VEGFR2 and MMP-2 expression compared with both the control and the single treatments.

Research Products

• [Journal Article] Novel HSP90 inhibitor NVP-AUY922 enhances the anti-tumor effect of temsirolimus against oral squamous cell carcinoma (2013)
  • Author(s): Okui T, Shimo T, Fukazawa T, Mohammad Monsur Hassan N, Honami T, Ibaragi S, Takaoka M, Naomoto Y, Sasaki A
  • Journal Title: Curr Cancer Drug Targets Volume: 13(3) Pages: 289-99
  • Peer Reviewed
• [Journal Article] Novel HSP90 Inhibitor NVP-AUY922 Enhances the Anti-tumor Effect of Temsirolimus Against Oral Squamous Cell Carcinoma. (2013)
  • Author(s): (Okui T), Shimo T, Fukazawa T, Mohammad Monsur Hassan N, Honami T, Ibaragi S, Takaoka M, Naomoto Y, Sasaki A.
  • Journal Title: Current cancer drug targets Volume: 13 Pages: 289-299
  • Peer Reviewed
• [Journal Article] Anti-tumor effect of a novel FAK inhibitor TAE226 against human oral squamous cell carcinoma. (2012)
  • Author(s): Kurio N, Shimo T, Fukazawa T, Okui T, Hassan NM, Honami T, Horikiri Y, Hatakeyama S, Takaoka M, Naomoto Y, Sasaki A.
  • Journal Title: Oral Oncol Volume: 48(11) Issue: 11 Pages: 1159-70
  • DOI: 10.1016/j.oraloncology.2012.05.019
  • Peer Reviewed
• [Journal Article] Hypoxia-induced up-regulation of angiogenin, besides VEGF, is related to progression of oral cancer. (2012)
  • Author(s): Kishimoto K, Yoshida S, Ibaragi S, Yoshioka N, Okui T, Hu GF, Sasaki A
  • Journal Title: Oral Oncol. Volume: 48(11) Issue: 11 Pages: 1120-7
  • DOI: 10.1016/j.oraloncology.2012.05.009
  • Peer Reviewed
• [Journal Article] Sonic hedgehog signaling promotes growth of oral squamous cell carcinoma cells associated with bone destruction. (2012)
  • Author(s): Honami T, Shimo T, Okui T, Kurio N, Hassan NM, Iwamoto M, Sasaki A
  • Journal Title: Oral Oncol Volume: 48(1) Issue: 1 Pages: 49-55
  • DOI: 10.1016/j.oraloncology.2011.08.026
  • Peer Reviewed
• [Journal Article] Antitumor effect of novel HSP90 inhibitor NVP-AUY922 against oral squamous cell carcinoma (2011)
  • Author(s): Okui T, Shimo T, Hassan NM, Fukazawa T, Kurio N, Takaoka M, Naomoto Y, Sasaki A
  • Journal Title: Anticancer Res Volume: 31(4) Pages: 1197-204
  • Peer Reviewed
• [Journal Article] Antitumor Effect of Novel HSP90 Inhibitor NVP-AUY922 against Oral Squamous Cell Carcinoma (2011)
  • Author(s): Tatsuo okui, et al
  • Journal Title: Anti cancer research Volume: 31 Pages: 1197-1204
  • Peer Reviewed
• [Presentation] 新規HSP90阻害薬NVP-AUY922はTemsirolimusの抗腫瘍効果を増強する (2011)
  • Author(s): 奥井達雄
  • Organizer: 第56回日本口腔外科学会総会学術集会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2011-10-22
• [Presentation] Antitumor effect of temsirolimus against oral squamous cell carcinoma associated with bone destruction
  • Author(s): 奥井達雄
  • Organizer: 岡山歯学会総会
  • Place of Presentation: 岡山
  • Invited