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

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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.

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Authors and Affiliations

  1. Southern Research Institute, 2000 9th Avenue South, Birmingham, Al, 35205

    Lisa Ann Kraus, Shanti K. Samuel, Steven M. Schmid, Donald J. Dykes & William R. Waud

  2. Aventis Oncology, 13, quai Jules Guesde –, BP 14, 94403, Vitry-sur-Seine, Cedex, France

    Marie Christine Bissery

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  1. Lisa Ann Kraus
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Kraus, L.A., Samuel, S.K., Schmid, S.M. et al. The mechanism of action of docetaxel (Taxotere®) in xenograft models is not limited to bcl-2 phosphorylation. Invest New Drugs 21, 259–268 (2003). https://doi.org/10.1023/A:1025436307913

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