Preferential chemosensitization of PTEN-mutated prostate cells by silencing the Akt kinase

Marcella Priulla, Angela Calastretti, Paola Bruno, Azzariti Amalia, Angelo Paradiso, Gianfranco Canti, Angelo Nicolin

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)782-789
Number of pages8
JournalProstate
Volume67
Issue number7
DOIs
Publication statusPublished - May 15 2007

Keywords

  • Akt
  • Chemosensitization
  • Prostate cancer
  • siRNA

ASJC Scopus subject areas

  • Urology

Fingerprint Dive into the research topics of 'Preferential chemosensitization of PTEN-mutated prostate cells by silencing the Akt kinase'. Together they form a unique fingerprint.

  • Cite this

    Priulla, M., Calastretti, A., Bruno, P., Amalia, A., Paradiso, A., Canti, G., & Nicolin, A. (2007). Preferential chemosensitization of PTEN-mutated prostate cells by silencing the Akt kinase. Prostate, 67(7), 782-789. https://doi.org/10.1002/pros.20566