Abstract
BACKGROUND. In prostate cancer, mutations of the phosphatase PTEN can activate the kinase cascade PI3K/Akt/mTOR which induces drug resistance. METHODS. Chemosensitization by siRNA targeting Akt was studied in HEK293 cells forced to express CA-Akt or kinase-dead DN-Akt. To decrease drug resistance, Akt was silenced with siRNA in human prostate DU-145 cell line expressing the normal PTEN or in LNCaP and PC3 cell lines expressing mutated-PTEN. Taxol was used for the chemosensitization studies. RESULTS. Silencing Akt in the drug-resistant CA-Akt cells efficiently sensitized cells to antitubule agents, whereas silencing drug-responsive DN-Akt cells did not. Only minor effects were obtained in wild-type HEK293 cells. Potentiation by siRNA of taxol cytotoxicity was significantly greater in mutated-PTEN cells than in prostate cells expressing wild-type PTEN. The apoptotic program induced by taxol was preferentially potentiated by Akt siRNA in PTEN-mutated cell lines as regards the DU-145 cell line. CONCLUSIONS. Silencing Akt in PTEN-mutated prostate cancer cells enhances the antitumor effects of taxol. No siRNA chemosensitization was obtained in prostate cells with wild type PTEN.
Original language | English |
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Pages (from-to) | 782-789 |
Number of pages | 8 |
Journal | Prostate |
Volume | 67 |
Issue number | 7 |
DOIs | |
Publication status | Published - May 15 2007 |
Keywords
- Akt
- Chemosensitization
- Prostate cancer
- siRNA
ASJC Scopus subject areas
- Urology