gms | German Medical Science

27. Deutscher Krebskongress

Deutsche Krebsgesellschaft e. V.

22. - 26.03.2006, Berlin

Enzastaurin, a Novel PKC-β Inhibitor, Inhibits Growth of Freshly Explanted Human Tumor Cells

Meeting Abstract

  • corresponding author presenting/speaker Olaf Oberschmidt - Allgemeines Krankenhaus St. Georg, Hamburg, Deutschland
  • Ulrike Eismann - Allgemeines Krankenhaus St. Georg, Hamburg
  • Michael Ehnert - Allgemeines Krankenhaus St. Georg, Hamburg
  • Jochen Fleeth - Allgemeines Krankenhaus St. Georg, Hamburg
  • Frank Erich Lüdtke - Allgemeines Krankenhaus St. Georg, Hamburg
  • Sakine Struck - Allgemeines Krankenhaus St. Georg, Hamburg
  • Lena Schulz - Allgemeines Krankenhaus St. Georg, Hamburg
  • Johannes Blatter - Eli Lilly & Co, Indianapolis
  • Michael M. Lahn - Eli Lilly & Co, Indianapolis
  • Doreen Ma - Eli Lilly & Co, Indianapolis
  • Axel-Rainer Hanauske - Allgemeines Krankenhaus St. Georg, Hamburg

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocPO453

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter:

Veröffentlicht: 20. März 2006

© 2006 Oberschmidt et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen ( Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.



Background: Enzastaurin (E; LY317615) is a novel cytotoxic agent targeted specifically against the beta-isoform of protein kinase C (PKC-beta). PKC-β is activated by polypeptide growth factors, eg VEGF, and directs numerous cell functions such as apoptosis, cell growth, and cell proliferation. These pathways are often abrogated by mutations in cancer cells and have been associated with tumorigenesis and carcinogenesis. The aim of the present study was to determine whether E exerts direct antiproliferative effects on freshly obtained human tumor cells in vitro.

Methods: Freshly biopsied tumor cells (solid tumors, pleural effusions, or ascites) were used for soft-agar cell cloning experiments. Cells were exposed to various concentrations of Enzastaurin based on plasma levels that are generally achieved in patients. Clonogenic tumor growth was evaluated after three weeks of cultivation. Tumor specimens were defined to be sensitive to E if colony formation was< 50 % of control.

Results: At present, 61 tumor specimens were analyzed for sensitivity to E. Antitumoral efficacy were observed in vitro for this agent against clonogenic cells especially derived from head/neck carcinoma, breast, thyroid, and pancreatic cancer at concentrations ranging from 14 to 1400 nM. Moderate cytotoxicity was observed in melanoma, mesothelioma, and bronchial cancer. These results indicate that E acts directly as anticancer agent. A concentration-dependent inhibition of colony formation was demonstrated for specimens exposed one hour or 21 days to E. Short term exposure (1-hour) experiments exhibited 22 % (12/54) inhibition at 14 nM, 18 % (10/56) at 140 nM, and 29 % (16/56) at 1400 nM E. In continuous exposure experiments, inhibition rates were: 18 % (11/60) at 14 nM, 21 % (13/61) at 140 nM, and 33 % (20/61) at 1400 nM.

Conclusions: These data indicate direct antitumor activity of E in vitro against freshly explanted tumor specimens. Colony formation was inhibited at nanomolar concentrations.

Supported in part by Eli Lilly & Company, USA

Table 1 [Tab. 1].