The role of mTOR and HSP90 against oral cancer induced angiogenesis

mTOR和HSP90对抗口腔癌诱导的血管生成的作用

• 批准号: 23890124
• 负责人: OKUI Tatsuo
• 金额: $ 2.08万
• 依托单位: Okayama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Research Activity Start-up
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-23890124/
• 关键词: HSP90; mTOR; 口腔癌; 血管新生; 癌血管新生

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.

在手术切除的下牙龈鳞状细胞癌样本中，CD31和VEGFR2在血管内皮细胞中高表达，VEGF-A在肿瘤细胞中表达。 HSP90抑制剂和mTOR抑制剂联合治疗比单独治疗更能显着抑制VEGF诱导的人脐静脉内皮细胞(HUVEC)的细胞增殖、管形成。明胶酶谱显示联合治疗比单独治疗更能抑制HUVEC中VEGF诱导的MMP-2活化。对移植有 SAS 口腔鳞状细胞癌细胞的小鼠进行的免疫组织化学分析显示，与单独治疗相比，给予 HSP90 抑制剂和 mTOR 抑制剂的小鼠肿瘤切片中 CD31 阳性肿瘤血管显着减少。此外，与对照和单一治疗相比，它们的联合治疗抑制了 VEGFR2 和 MMP-2 的表达。

项目成果

Novel HSP90 Inhibitor NVP-AUY922 Enhances the Anti-tumor Effect of Temsirolimus Against Oral Squamous Cell Carcinoma

• DOI: 10.2174/1568009611313030007
• 发表时间: 2013-03-01
• 期刊: CURRENT CANCER DRUG TARGETS
• 影响因子: 3
• 作者: Okui, Tatsuo;Shimo, Tsuyoshi;Sasaki, Akira
• 通讯作者: Sasaki, Akira

新規HSP90阻害薬NVP-AUY922はTemsirolimusの抗腫瘍効果を増強する

新型HSP90抑制剂NVP-AUY922增强替西罗莫司的抗肿瘤作用

• 发表时间: 2011
• 作者: Fukushima H.;Kawanabe N.;Murata S.;et al.;奥井達雄
• 通讯作者: 奥井達雄

Antitumor effect of novel HSP90 inhibitor NVP-AUY922 against oral squamous cell carcinoma

新型HSP90抑制剂NVP-AUY922对口腔鳞癌的抗肿瘤作用

• 发表时间: 2011
• 期刊: Anticancer Res
• 影响因子: 2
• 作者: Okui T;Shimo T;Hassan NM;Fukazawa T;Kurio N;Takaoka M;Naomoto Y;Sasaki A
• 通讯作者: Sasaki A

Antitumor Effect of Temsirolimus against Oral Squamous Cell Carcinoma Associated with Bone Destruction

• DOI: 10.1158/1535-7163.mct-10-0489
• 发表时间: 2010-11-01
• 期刊: MOLECULAR CANCER THERAPEUTICS
• 影响因子: 5.7
• 作者: Okui, Tatsuo;Shimo, Tsuyoshi;Sasaki, Akira
• 通讯作者: Sasaki, Akira