Tissue factor‑targeted lidamycin inhibits growth and metastasis of colon carcinoma

Zhang,Qing; Liu,Xiujun; Li,Caihong; Liao,Dongsheng; Ouyang,Zhigang; Zheng,Junnian; Song,Xu

doi:10.3892/ol.2013.1437

Tissue factor‑targeted lidamycin inhibits growth and metastasis of colon carcinoma

Authors:
- Qing Zhang
- Xiujun Liu
- Caihong Li
- Dongsheng Liao
- Zhigang Ouyang
- Junnian Zheng
- Xu Song
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Affiliations: Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, P.R. China, Center for Functional Genomics and Bioinformatics, College of Life Science, Sichuan University, Chengdu, Sichuan 610064, P.R. China
Published online on: July 3, 2013 https://doi.org/10.3892/ol.2013.1437
Pages: 801-806

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Abstract

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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