Investigational New Drugs

, Volume 21, Issue 3, pp 259–268

The mechanism of action of docetaxel (Taxotere®) in xenograft models is not limited to bcl-2 phosphorylation

Authors

  • Lisa Ann Kraus
    • Southern Research Institute
  • Shanti K. Samuel
    • Southern Research Institute
  • Steven M. Schmid
    • Southern Research Institute
  • Donald J. Dykes
    • Southern Research Institute
  • William R. Waud
    • Southern Research Institute
  • Marie Christine Bissery
    • Aventis Oncology
Article

DOI: 10.1023/A:1025436307913

Cite this article as:
Kraus, L.A., Samuel, S.K., Schmid, S.M. et al. Invest New Drugs (2003) 21: 259. doi:10.1023/A:1025436307913

Abstract

Docetaxel is a new taxoid compound with a broad spectrum of antitumor activity. Previous studies have shown that in vitro treatment of specific human tumor lines with docetaxel is associated with the phosphorylation and inactivation of the bcl-2 protein and the occurrence of apoptosis. The goal of this study was to examine whether bcl-2 expression is truly required for in vivo responsiveness to docetaxel. The expression and state of phosphorylation of bcl-2 was examined in human MX-1 breast or DU-145 prostate tumors explanted from nu/nu mice treated with docetaxel. The MX-1 cells accumulated in the G2/M phase of the cell cycle and exhibited phosphorylation of bcl-2 after treatment with docetaxel. By Western blot analysis DU-145 prostate tumor cells did not express bcl-2 protein before or following in vivo treatment with docetaxel. However, docetaxel was highly active against the DU-145 tumor xenograft model. Thus, docetaxel induces apoptosis and cell death through a different, bcl-2-independent mechanism in the DU-145 human prostate tumor, indicating that bcl-2 may not have prognostic value for treatment with docetaxel.

bcl-2docetaxelTaxotere®xenografts

Copyright information

© Kluwer Academic Publishers 2003