Suppression of ErbB-2 in androgen-independent human prostate cancer cells enhances cytotoxic effect by gemcitabine in an androgen-reduced environment

Li Zhang, Jeffrey S. Davis, Stanislav Zelivianski, Fen Fen Lin, Rachel Schutte, Thomas L. Davis, Ralph Hauke, Surinder Kumar Batra, Ming-Fong Lin

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

We examined the efficacy of combination treatments utilizing cytotoxic drugs plus inhibitors to members of the ErbB-ERK signal pathway in human prostate cancer (PCa) LNCaP C-81 cells. Under an androgen-reduced condition, 50 nM gemcitabine caused about 40% growth suppression on C-81 cells. Simultaneous treatment of gemcitabine plus 10 μM AG825 produced 60% suppression (p < 0.03); while, 85% growth inhibition (p < 0.02) was seen if AG825 was added to gemcitabine-treated cells after a 24 h-interval. Our data thus showed that in androgen-reduced conditions, inhibition of ErbB-2 increases the cytotoxic efficacy of gemcitabine in PCa cells. This finding has significant implications in the choice of drugs for combination therapy as well as the order of administration for treating cancer patients.

Original languageEnglish (US)
Pages (from-to)58-65
Number of pages8
JournalCancer Letters
Volume285
Issue number1
DOIs
StatePublished - Nov 18 2009

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Keywords

  • Combination therapy
  • ErbB-2 inhibitor
  • Gemcitabine
  • Hormone-refractory prostate cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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