Colorectal Cancer
Copyright ©2007 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. May 7, 2007; 13(17): 2484-2489
Published online May 7, 2007. doi: 10.3748/wjg.v13.i17.2484
Synergistic anti-tumor effect of recombinant chicken fibroblast growth factor receptor-1-mediated anti-angiogenesis and low-dose gemcitabine in a mouse colon adenocarcinoma model
Shao-Jiang Zheng, Shao-Ping Zheng, Feng-Ying Huang, Chang-Liang Jiao, Ren-Liang Wu
Shao-Jiang Zheng, Ren-Liang Wu, Department of Pathology, Tongji Medical College, Huazhong University of Science and Technology; Pulmonary Disease Laboratory, The Ministry of Health of China, Wuhan 430030, Hubei Province, China
Shao-Jiang Zheng, Chang-Liang Jiao, Department of Pathology, Hainan Medical College and The Affiliated Hospital, Haikou 571101, Hainan Province, China
Shao-Ping Zheng, Department of Ultrasonography, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
Shao-Ping Zheng, Feng-Ying Huang, Hainan Province Key Laboratory of Tropical Medicine, Hainan Medical College, Haikou 571101, Hainan Province, China
Author contributions: All authors contributed equally to the work.
Supported by the Natural Sciences Foundation of Hainan Province, No. 30321 and partly supported by the National Natural Sciences Foundation of China, No. 30660055
Correspondence to: Ren-Liang Wu, Department of Pathology, Tongji Medical College, Huazhong University of Science and Technology; Pulmonary Disease Laboratory, The Ministry of Health of China,Wuhan 430030, Hubei Province, China.
Telephone: +86-27-83691894 Fax: +86-27-83691894
Received: December 2, 2006
Revised: December 8, 2006
Accepted: March 1, 2007
Published online: May 7, 2007

AIM: To evaluate whether the combination of recom-binant chicken fibroblast growth factor receptor -1 (FGFR-1) protein vaccine (cFR-1) combined with low-dose gemcitabine would improve anti-tumor efficacy in a mouse CT26 colon adenocarcinoma (CT26) model.

METHODS: The CT26 model was established in BABL/c mice. Seven days after tumor cell injection, mice were randomly divided into four groups: combination therapy, cFR-1 alone, gemcitabine alone, and normal saline groups. Tumor growth, survival rate of tumor-bearing mice, and systemic toxicity were observed. The presence of anti-tumor auto-antibodies was detected by Western blot analysis and enzyme-linked immunospot assay, microvessel density (MVD) of the tumors and tumor cell proliferation were detected by Immunohistochemistry staining, and tumor cell apoptosis was detected by TdT-mediated biotinylated-dUTP nick end label staining.

RESULTS: The combination therapy results in apparent decreases in tumor volume, microvessel density and tumor cell proliferation, and an increase in apoptosis without obvious side-effects as compared with either therapy alone or normal control groups. Also, both auto-antibodies and the antibody-producing B cells against mouse FGFR-1 were detected in mice immunized with cFR-1 vaccine alone or with combination therapy, but not in non-immunized mice. In addition, the deposition of auto-antibodies on endothelial cells from mice immunized with cFR-1 was observed by immunofluorescent stain-ing, but not on endothelial cells from control groups. Synergistic indexes of tumor volume, MVD, cell apoptosis and proliferation in the combination therapy group were 1.71 vs 1.15 vs 1.11 and 1.04, respectively, 31 d after tumor cell injection.

CONCLUSION: The combination of cFR-1-mediated anti-angiogenesis and low-dose gemcitabine synergistically enhances the anti-tumor activity without overt toxicity in mice.

Keywords: Fibroblast growth factor receptor-1, Gemcitabine, Anti-angiogenesis, Vaccine, Combination therapy