In vitro and in vivo antitumor activity of the phosphatidylinositol-3-kinase inhibitor, wortmannin.
Anticancer Res
; 15(4): 1135-9, 1995.
Article
em En
| MEDLINE
| ID: mdl-7653991
ABSTRACT
The microbial product wortmannin has previously been shown to be a potent inhibitor of phosphatidylinositol-3-kinase. In view of the potential role of this enzyme in transduction of mitogenic signals, we determined the cytotoxic activity of wortmannin against several human tumor cell lines in vitro. The most sensitive lines included GC3 colon carcinoma, IGROV1 ovarian carcinoma, and CCRF-CEM leukemia (IC-50s ranging from 0.7-2.1 microM). The cytotoxicity of wortmannin was decreased approximately 10-fold by serum-free conditions. Wortmannin was generally less active in low passage human breast cancer cell lines that overexpress either epidermal growth factor receptor or Her2/neu. Wortmannin was also tested for in vivo antitumor activity against seven murine tumor and ten human tumor xenograft models. Activity (> 60% inhibition of tumor growth) was observed in only the C3H mammary carcinoma and the human BxPC-3 pancreatic carcinoma xenograft. In vivo antitumor activity did not correlate with in vitro sensitivity to wortmannin cytotoxicity.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfotransferases (Aceptor do Grupo Álcool)
/
Androstadienos
/
Antineoplásicos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Anticancer Res
Ano de publicação:
1995
Tipo de documento:
Article
País de afiliação:
Estados Unidos