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In vitro and in vivo effects of repifermin (keratinocyte growth factor-2, KGF-2) on human carcinoma cells

In vitro and in vivo effects of repifermin (keratinocyte growth factor-2, KGF-2) on human carcinoma cells. Alderson, Ralph; Gohari-Fritsch, Shiva; Olsen, Hendrik; Roschke, Viktor; Vance, Courtney; Connolly, Kevin (Human Genome Sciences, Inc., Rockville, MD 20850, USA). Cancer Chemotherapy and Pharmacology, 50(3), 202-212 (English) 2002 Springer-Verlag. CODEN: CCPHDZ. ISSN: 0344-5704. DOCUMENT TYPE: Journal CA Section: 2 (Mammalian Hormones) Section cross-reference(s): 14 Repifermin (keratinocyte growth factor-2, KGF-2) is a growth factor that selectively induces epithelial cell proliferation, differentiation and migration. The objective of this study was to assess the effect of repifermin on in vitro tumor cell proliferation and in vivo tumor growth using a variety of human carcinoma cell lines with differing growth rates and levels of KGF receptor (KGFR) expression. Potential effects of repifermin on in vitro cell proliferation were evaluated by alamarBlue and/or [3H]-thymidine incorporation assays under a range of serum conditions. In vivo tumor growth was evaluated by implanting KGFR+ carcinomas s.c.There are some reagents like 219527-63-6 is used in this study. into nude mice and measuring tumor growth over time in mice injected i.v. or i.p. with repifermin or placebo. In vitro, none of the 30 human carcinoma cell lines tested demonstrated a substantial increase in proliferation in response to repifermin over the concn. range 0.01 to 1000 ng/mL. In vivo results showed no significant tumor growth-promoting activity when single- or multiple-cycle i.v. injections of repifermin (1 mg/kg) were given to athymic nude mice inoculated with human KGFR+ tumors of the pharynx (Detroit 562, FaDu), colon (Caco-2), salivary gland (A-253) or tongue (SCC-25, CAL 27). In addn., repifermin (0.2 or 2 mg/kg) injected i.p. for 2 wk had no effect on the growth of eight other human carcinomas including those of the ovary (NIH:OVCAR-3, SK-OV 3, PA-1), bladder (SCaBER), epidermis (A 431), lung (SW 900), breast (MDA-MB-231) and cervix (SiHa). Thus, repifermin had no in vitro or in vivo proliferative effects on KGFR+ human epithelial-like tumors. This failure to stimulate tumor cell growth highlights the ability of repifermin to specifically target normal epithelial tissue. This is crit. to the safety profile of repifermin, since it is currently in phase II clin. trials for the treatment of cancer patients with mucositis resulting from chemo- or radiotherapy. .