The mechanism of action of docetaxel (Taxotere) in xenograft models is not limited to bcl-2 phosphorylation.
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.
Kraus
Lisa Ann
LA
Southern Research Institute, 2000 9th Avenue South, Birmingham, Al 35205, USA.
Samuel
Shanti K
SK
Schmid
Steven M
SM
Dykes
Donald J
DJ
Waud
William R
WR
Bissery
Marie Christine
MC
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001943:Breast Neoplasms; D002453:Cell Cycle; D000077143:Docetaxel; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism; D010766:Phosphorylation; D011471:Prostatic Neoplasms; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D043823:Taxoids / Q000494:pharmacology* / Q000627:therapeutic use; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D019253:Proto-Oncogene Proteins c-bcl-2; D043823:Taxoids; D000077143:Docetaxel