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

Invest New Drugs. 2003 Aug;21(3):259-68. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Apoptosis / drug effects
  • Blotting, Western
  • Breast Neoplasms
  • Cell Cycle
  • Docetaxel
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Neoplasms, Experimental / drug therapy*
  • Neoplasms, Experimental / metabolism
  • Phosphorylation
  • Prostatic Neoplasms
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Taxoids / pharmacology*
  • Taxoids / therapeutic use
  • Transplantation, Heterologous
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents, Phytogenic
  • Proto-Oncogene Proteins c-bcl-2
  • Taxoids
  • Docetaxel