A fusion protein containing murine vascular endothelial growth factor and tissue factor induces thrombogenesis and suppression of tumor growth in a colon carcinoma model
A fusion protein containing murine vascular endothelial growth factor and tissue factor induces thrombogenesis and suppression of tumor growth in a colon carcinoma model
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含有鼠血管内皮生长因子和组织因子的融合蛋白在结肠癌模型中诱导血栓形成并抑制肿瘤生长
DOI：
10.1631/jzus.b0820120
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发表时间：
2008-08-01
影响因子：
5.1
通讯作者：
Tan, Guang-hong
中科院分区：
文献类型：
--
作者：
Huang, Feng-ying;Li, Yue-nan;Tan, Guang-hong
通过靶向血栓原在肿瘤组织中新形成的血管诱导肿瘤血管闭塞代表了根除原发性实体肿瘤的一个有趣的方法。在本研究中，我们构建并表达了一种含有血管内皮生长因子（VEGF）和组织因子（TF）的融合蛋白，探讨该融合蛋白在结肠癌模型中是否具有抑制肿瘤生长的能力。采用逆转录聚合酶链式反应（RT-PCR）扩增小鼠VEGF A和TF cDNA，并将其克隆到带连接子的原核表达质粒pQE30中。表达产物重组VEGF-TF （rVEGF-TF）被纯化，并被证明具有与商业TF相当的酶活性和特异性结合肿瘤血管的能力。在rVEGF-TF开始治疗后的第6天，给予rVEGF-TF的小鼠肿瘤生长明显减少（P<0.05），第14天，10只小鼠中有2只肿瘤肿块几乎消失。此外，在注射rVEGF-TF的肿瘤组织中观察到有效的血栓形成和肿瘤坏死。我们的研究结果表明，用rVEGF-TF阻断肿瘤血管是一种潜在的有效的癌症治疗方法。
Induction of tumor vasculature occlusion by targeting a thrombogen to newly formed blood vessels in tumor tissues represents an intriguing approach to the eradication of primary solid tumors. In the current study, we construct and express a fusion protein containing vascular endothelial growth factor (VEGF) and tissue factor (TF) to explore whether this fusion protein has the capability of inhibiting tumor growth in a colon carcinoma model. The murine cDNA of VEGF A and TF were amplified by reverse transcriptase polymerase chain reaction (RT-PCR), and then cloned into prokaryotic expression plasmid pQE30 with a linker. The expression product recombinant VEGF-TF (rVEGF-TF) was purified and proved to have comparable enzyme activity to a commercial TF and the capability of specific binding to tumor vessels. Significant decrease of tumor growth was found in the mice administered with rVEGF-TF on Day 6 after initiated rVEGF-TF treatment (P<0.05), and the tumor masses in 2 of 10 mice were almost disappeared on Day 14 after the first treatment. In addition, valid thrombogenesis and tumor necrosis were observed in the tumor tissues injected with rVEGF-TF. Our results demonstrate that occlusion of tumor vasculature with rVEGF-TF is potentially an effective approach for cancer therapy.