Development of molecular target therapy to VEGF and VEGFR against oral cancer with RNAi methods

RNAi方法开发针对口腔癌的VEGF和VEGFR分子靶向治疗

• 批准号: 17592084
• 负责人: KOIZUMI Koichi
• 金额: $ 2.3万
• 依托单位: HIROSHIMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17592084/
• 关键词: oral cancer; VEGF; molecular target therapy

Cell migration plays a significant role in cancer invasion and metastasis. Our previous studies have shown vascular endothelial growth factor ( VEGF) and VEGF receptor 1 ( Flt-1 ) express in oral squamous cell carcinoma ( SCC ) cells. These finding suggests VEGF-VEGFR system might regulate in autocrine manner as well as angiogenesis in paracrine manner.In this study, we examined the expression of VEGF and VEGFR in melanoma cells. The participation of VEGF and VEGFR in invasion and metastasis of melanoma cells was also investigated.VEGF-induced proliferation of melanoma cells were suppressed by VEGFR-1 antisense oligo, but not by VEGFR-2 antisense oligo.Checkerbord analysis showed that VEGF induced Chemotaxitic and Chemokinetic migration in melanoma cells. The VEGF-induced migration was inhibited by VEGFR tyrosine kinase inhibitor. The migration was suppressed by VEGFR-1 antisense oligo, but not by VEGFR-2 antisense oligo.VEGF induced phosphorilation of Akt. PI3 kinase inhibitor block the VEGF-induced phosphorilation of PI3/Akt kinase cascade, and suppressed VEGF-induced motility of melanoma cells. These findings suggest that migration of melanoma cells is regulated with VEGF-induced activation of PI3/Akt kinase cascade

细胞迁移在肿瘤的侵袭和转移中起着重要作用。我们先前的研究表明，口腔鳞状细胞癌(SCC)细胞表达血管内皮生长因子(VEGF)及其受体1(Flt-1)。这些发现表明，VEGF-VEGFR系统可能以自分泌方式调节血管生成，也可能以旁分泌方式调节血管生成。VEGFR-1反义寡核苷酸能抑制VEGFR-1反义寡核苷酸诱导的黑色素瘤细胞增殖，而VEGFR-2反义寡核苷酸不能抑制VEGFR-2反义寡核苷酸诱导的黑色素瘤细胞增殖。Checkerbord分析表明，VEGFR-1反义寡核苷酸可诱导黑色素瘤细胞趋化和趋化迁移。VEGFR酪氨酸激酶抑制剂可抑制血管内皮生长因子诱导的细胞迁移。VEGFR-1反义寡核苷酸可抑制Akt的迁移，而VEGFR-2反义寡核苷酸不能抑制其迁移。PI3激酶抑制剂阻断了血管内皮生长因子诱导的PI3/Akt激酶通路的磷酸化，并抑制了血管内皮生长因子诱导的黑色素瘤细胞的运动。这些发现表明，黑色素瘤细胞的迁移受血管内皮生长因子诱导的PI3/Akt激酶级联反应的调节

项目成果

ヒトメラノーマ細胞におけるVEGF受容体系の機能解析

人黑色素瘤细胞VEGF受体系统的功能分析

• 发表时间: 2005
• 期刊: 口腔組織培養学会誌 14巻・1号
• 作者: Yoshioka;Y;夏目長門編;Hitoshi Nagatsuka;Hitoshi Nagatsuka;Tamatani T;Tamatani T;Tamatani T;小泉 浩一
• 通讯作者: 小泉 浩一

Pole of Vascular Endothelial Growth Factor Receptor System in the motility of Human Melanoma Cell Lines

血管内皮生长因子受体系统在人黑色素瘤细胞系运动中的极点

• 发表时间: 2005
• 期刊: The Japanese Journal of Tissue Culture Society for Dental Research 14 (1)
• 作者: Yoshioka;Y;夏目長門編;Hitoshi Nagatsuka;Hitoshi Nagatsuka;Tamatani T;Tamatani T;Tamatani T;小泉 浩一;Koichi Koizumi
• 通讯作者: Koichi Koizumi