A Gelatinases-targeting scFv-based Fusion Protein Shows Enhanced Antitumour Activity with Endostar against Hepatoma
| Autor: | Liang Li, Rui-Juan Gao, Chunyan Zhao, Boyang Shang, Dian-Dong Li, Weijin Sheng |
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| Rok vydání: | 2015 |
| Předmět: |
Gelatinases
Carcinoma Hepatocellular Lung Neoplasms Mice Nude Angiogenesis Inhibitors Biology Toxicology Metastasis Mice Gentamicin protection assay In vivo Cell Line Tumor medicine Animals Humans Secretion Pharmacology Mice Inbred BALB C Liver Neoplasms Carcinoma Giant Cell Drug Synergism General Medicine medicine.disease Xenograft Model Antitumor Assays Molecular biology Fusion protein Recombinant Proteins Endostatins Angiogenesis inhibitor Aminoglycosides Cell culture Female Enediynes Apoproteins Single-Chain Antibodies |
| Zdroj: | Basic & Clinical Pharmacology & Toxicology. 117:105-116 |
| ISSN: | 1742-7835 |
| DOI: | 10.1111/bcpt.12379 |
| Popis: | Gelatinases play important roles in tumour invasion and metastasis and are thus considered promising targets for cancer therapy. In this study, a new single-chain variable fragment (scFv)-based fusion protein Fv-LDP, composed of the anti-gelatinases scFv and lidamycin apoprotein (LDP), was prepared, and its combination with angiogenesis inhibitor Endostar was then investigated. The fusion protein Fv-LDP specifically bound to various tumour cells, and its binding capability to human pulmonary giant cell carcinoma (PG) cells was higher than that of LDP. Fv-LDP inhibited the expression and secretion of gelatinases and could be internalized into tumour cells via endocytosis. Fv-LDP also suppressed the growth of human hepatoma cells and murine hepatoma 22 transplanted in Kunming mice in various degrees. In addition, Endostar could enhance the synergistic or additive inhibition of Fv-LDP on the growth, migration or invasion of human hepatoma cells shown by a colony formation assay and a transwell-based migration or invasion assay, respectively. In vivo, Fv-LDP/Endostar combination showed a significantly synergistic effect on the growth of a human hepatoma xenograft, with an inhibition rate of 80.8% compared with the Fv-LDP (44.1%) or Endostar (8.9%)-treated group. The above-mentioned results indicate that the fusion protein Fv-LDP is effective against transplantable hepatoma in mice and human hepatoma xenografts in athymic mice. Moreover, Endostar can potentiate the inhibition effect of Fv-LDP on the growth of human hepatoma cells and xenografts. These data will provide a new combined strategy for improving the therapeutic efficacy of treatments for hepatoma or other gelatinase-overexpressing tumours. |
| Databáze: | OpenAIRE |
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