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In vitro and in vivo antitumor activity of the phosphatidylinositol-3-kinase inhibitor, wortmannin.

Authors
  • Schultz, R M1
  • Merriman, R L
  • Andis, S L
  • Bonjouklian, R
  • Grindey, G B
  • Rutherford, P G
  • Gallegos, A
  • Massey, K
  • Powis, G
  • 1 Division of Cancer Research, Lilly Research Laboratories, Indianapolis, IN 46285, USA. , (India)
Type
Published Article
Journal
Anticancer research
Publication Date
Jan 01, 1995
Volume
15
Issue
4
Pages
1135–1139
Identifiers
PMID: 7653991
Source
Medline
Language
English
License
Unknown

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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