Cytotoxicity of a novel fibroblast growth factor receptor targeted immunotoxin on a human ovarian teratocarcinoma cell line.
Basic fibroblast growth factor (bFGF) is an important tumor-associated growth factor that contributes to proliferation and angiogenesis of tumor. The high-affinity receptor for bFGF, fibroblast growth factor receptor (FGFR), is found to be overexpressed in a number of tumor cells. For the purpose of exploring the significance of bFGF/FGFR in tumor-targeted therapy, a recombinant immunotoxin contained the N-terminal 389 residues of diphtheria toxin (DT), and the full length of human bFGF was designed, expressed, and purified. The bioactivity of the product was evaluated by testing the cytotoxicity on PA-1 cells (a human ovarian teratocarcinoma cell line with high-level expression of FGFR) in vitro. The immunotoxin showed a significant cytotoxicity on PA-1 cells (IC(50) 8 - 9 ng/mL), and this effect could be antagonized by equine diphtheria antitoxin (DAT), bFGF, anti-bFGF monoclonal antibody (MAb), and anti- FGFR polyclonal antibody (PAb), respectively. Additionally, Chinese hamster ovary (CHO) cells and Hep-2 cells (a human epidermoid laryngocarcinoma cell line) with low expression of FGFR were tested to be resistant to the immunotoxin. The results indicated that FGFR might be an effective target for tumor therapy, and bFGF-mediated immunotoxin could be a potential candidate in the treatment of cancer.
Zhang
Huajie
H
Microbiology Department, Peking University Health Science Center, Beijing, China.
Zhang
Shumin
S
Zhuang
Hui
H
Lu
Fengmin
F
D000818:Animals; D015153:Blotting, Western; D016466:CHO Cells; D045744:Cell Line, Tumor; D006224:Cricetinae; D003602:Cytotoxicity, Immunologic; D004167:Diphtheria Toxin / Q000008:administration & dosage* / Q000276:immunology; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D006801:Humans; D000922:Immunotoxins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D018243:Teratocarcinoma / Q000276:immunology / Q000378:metabolism / Q000628:therapy*
D004167:Diphtheria Toxin; D000922:Immunotoxins; D017468:Receptors, Fibroblast Growth Factor; D011993:Recombinant Fusion Proteins; D016222:Fibroblast Growth Factor 2