Short interfering RNA vectors against VEGF-C and VEGF-A suppress lymphatic metastasis and lymphatic metastasis of mammary cancer model

抗VEGF-C和VEGF-A的短干扰RNA载体抑制乳腺癌模型的淋巴转移和淋巴转移

• 批准号: 17591360
• 负责人: SHIBATA Masa-aki
• 金额: $ 2.3万
• 依托单位: Osaka Medical College
• 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-17591360/
• 关键词: siRNA; VEGF-C; VEGF-A; Lymphatic metastasis; hematogeneous metastasis; Mammary carcioma; Metastasis; mouse; Lymphangiogenesis; Angiogenesis; Metastasis; Mammary cancer; Mouse

Human breast cancers metastasize mainly to the lymph nodes, lungs, and intractable metastasis leads to death. VEGF-C expression has been shown to correlate with lymph node metastasis in a variety of human cancers. VEGF-A has also been reported to participate on hematogeneous metastasis. Syngeneic inoculated metastatic mammary cancers received direct intratumoral injection of psiRNA-SCR control vector, psiRNA-VEGF-C vector, psiRNA-VEGF-A or their combination once a week for 8 weeks. We applied electrogene transfer to the tumors after each injection. Tumor volume was significantly lower in the psiRNA-VEGF-A and the combination groups as compared to the control group. Both incidence and multiplicity of the lymph node metastasis were significantly less frequent in all therapeutic groups. While incidence of the lung metastasis in all groups was similar, the number of lung metastatic foci was significantly decreased in the combination group only. In addition, the numbers of dilated lymphatic vessels containing intaluminal tumor cells were significantly decreased in all therapeutic groups. Our data suggest that not only VEGF-C but also VEGF-A correlate to lymphatic metastasis, and the observed anti-metastasis activity of siRNA against VEGF-C and VEGF-A may be of high clinical significance in the treatment of metastatic breast cancer.

人类乳腺癌主要转移至淋巴结、肺部，顽固性转移会导致死亡。 VEGF-C 表达已被证明与多种人类癌症的淋巴结转移相关。 VEGF-A 也被报道参与血行转移。同基因接种的转移性乳腺癌接受直接瘤内注射psiRNA-SCR对照载体、psiRNA-VEGF-C载体、psiRNA-VEGF-A或其组合，每周一次，持续8周。每次注射后我们将电基因转移到肿瘤上。与对照组相比，psiRNA-VEGF-A 组和联合组的肿瘤体积显着降低。在所有治疗组中，淋巴结转移的发生率和多重性均显着降低。虽然所有组中肺转移的发生率相似，但仅联合组中肺转移灶的数量显着减少。此外，所有治疗组中含有管腔内肿瘤细胞的扩张淋巴管的数量均显着减少。我们的数据表明，不仅VEGF-C而且VEGF-A都与淋巴转移相关，观察到的针对VEGF-C和VEGF-A的siRNA的抗转移活性可能在转移性乳腺癌的治疗中具有很高的临床意义。

项目成果

移転性乳癌モデルを用いた実験的癌治療の試み-脈管を標的とした癌遺伝子治療-

使用转移性乳腺癌模型进行实验性癌症治疗 - 针对血管的癌症基因治疗 -

• 发表时间: 2007
• 期刊: 大阪医科大学雑誌 65・3
• 作者: Hiromichi Kawaida;Koji Kono;Hidemitsu Sugai;et al.;柴田雅朗;柴田雅朗
• 通讯作者: 柴田雅朗

転移性乳癌モデルを用いた実験的乳癌治療の試み-脈管を標的とした癌遺伝子治療-

使用转移性乳腺癌模型进行实验性乳腺癌治疗 - 针对血管的癌症基因治疗 -

• 发表时间: 2007
• 期刊: 大阪医科大学雑誌 65・3
• 作者: Hiromichi Kawaida;Koji Kono;Hidemitsu Sugai;et al.;柴田雅朗
• 通讯作者: 柴田雅朗