Investigational New Drugs

, Volume 21, Issue 3, pp 259-268

First online:

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

  • Lisa Ann KrausAffiliated withSouthern Research Institute
  • , Shanti K. SamuelAffiliated withSouthern Research Institute
  • , Steven M. SchmidAffiliated withSouthern Research Institute
  • , Donald J. DykesAffiliated withSouthern Research Institute
  • , William R. WaudAffiliated withSouthern Research Institute
  • , Marie Christine BisseryAffiliated withAventis Oncology

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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-2 docetaxel Taxotere® xenografts