期刊
INVESTIGATIONAL NEW DRUGS
卷 21, 期 3, 页码 259-268出版社
SPRINGER
DOI: 10.1023/A:1025436307913
关键词
bcl-2; docetaxel; Taxotere (R); xenografts
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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