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

Autor: Kraus LA; Southern Research Institute, 2000 9th Avenue South, Birmingham, Al 35205, USA., Samuel SK, Schmid SM, Dykes DJ, Waud WR, Bissery MC
Jazyk: angličtina
Zdroj: Investigational new drugs [Invest New Drugs] 2003 Aug; Vol. 21 (3), pp. 259-68.
DOI: 10.1023/a:1025436307913
Abstrakt: 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.
Databáze: MEDLINE