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
| Autor: | Shao-Jiang Zheng, Fengying Huang, Ren-Liang Wu, Shao-Ping Zheng, Chang-Liang Jiao |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Antimetabolites
Antineoplastic Pathology medicine.medical_specialty animal structures Combination therapy Apoptosis Adenocarcinoma Cancer Vaccines Deoxycytidine Mice Random Allocation Animals Medicine Cell Proliferation Colorectal Cancer Mice Inbred BALB C Mouse Colon Adenocarcinoma Dose-Response Relationship Drug Neovascularization Pathologic business.industry Cell growth Fibroblast growth factor receptor 1 Gastroenterology Drug Synergism General Medicine medicine.disease Gemcitabine Recombinant Proteins Survival Rate Disease Models Animal Fibroblast growth factor receptor embryonic structures Colonic Neoplasms Cancer research Fibroblast Growth Factor 1 business Chickens medicine.drug |
| Zdroj: | World Journal of Gastroenterology. 13:2484 |
| ISSN: | 1007-9327 |
| DOI: | 10.3748/wjg.v13.i17.2484 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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