Tissue factor-targeted lidamycin inhibits growth and metastasis of colon carcinoma.
Tissue factor-targeted lidamycin inhibits growth and metastasis of colon carcinoma.
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DOI：
10.3892/ol.2013.1437
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发表时间：
2013-09
期刊：
影响因子：
2.9
通讯作者：
Song X
中科院分区：
文献类型：
--
作者：
Zhang Q;Liu X;Li C;Liao D;Ouyang Z;Zheng J;Song X
结肠癌是世界上第三大常见癌症。结肠癌细胞中组织因子（TF）的过度表达使其成为结肠癌治疗的理想靶点。本研究的目的是开发一种 TF 靶向赋能融合蛋白 mlFVII-LDP-AE，它由作为靶向结构域的小鼠 VII 因子轻链 (mlFVII) 与作为效应结构域的高细胞毒性抗生素力达霉素 (LDM、LDP-AE) 缀合组成。在小鼠结肠癌皮下异种移植模型和 BALB/c 小鼠的活转移模型中测试了 mlFVII-LDP-AE 对于小鼠结肠癌治疗的潜在功效。 mlFVII-LDP-AE显示出91.2%的肿瘤生长抑制率（在0.8mg/kg的剂量下）和84.7%的肿瘤转移抑制率（在0.6mg/kg的剂量下）。结果表明mlFVII-LDP-AE能够有效抑制小鼠结肠癌的生长和转移。由于人TF和FVII具有与小鼠相似的特征，因此人FVII轻链(hFVII)靶向的LDM(hFVII-LDP-AE)有望具有治疗人结肠癌的潜力。
Colon cancer is the third most common cancer in the world. The overexpression of tissue factor (TF) in colon cancer cells makes it an ideal target for colon cancer therapy. The purpose of the present study was to develop a TF-targeting energized fusion protein, mlFVII-LDP-AE, which is composed of a mouse Factor VII light chain (mlFVII) as the targeting domain conjugated to the highly cytotoxic antibiotic lidamycin (LDM, LDP-AE) as the effector domain. The potential efficacy of mlFVII-LDP-AE for mouse colon cancer therapy was tested in a mouse colon cancer subcutaneous xenograft model and a live metastasis model in BALB/c mice. mlFVII-LDP-AE showed a tumor growth inhibition rate of 91.2% (at a dose of 0.8 mg/kg) and a tumor metastasis inhibition rate of 84.7% (at a dose of 0.6 mg/kg). The results showed that mlFVII-LDP-AE was able to effectively inhibit the growth and metastasis of mouse colon cancer. As human TF and FVII have features similar to those of mice, human FVII light chain (hlFVII)-targeted LDM (hlFVII-LDP-AE) may be expected to have therapeutic potential for human colon cancer.
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影响因子：
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作者：
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通讯作者：
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