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Suppression of ErbB-2 in androgen-independent human prostate cancer cells enhances cytotoxic effect by gemcitabine in an androgen-reduced environment |
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| Authors: | Li Zhang Jeffrey S. Davis Stanislav Zelivianski Fen-Fen Lin Rachel Schutte Thomas L. Davis Ralph Hauke Surinder K. Batra Ming-Fong Lin |
| Affiliation: | 1. Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA;2. Nebraska Health System University Hospital, University of Nebraska Medical Center, Omaha, NE, USA;3. Department of Internal Medicine, College of Medicine and Nebraska Cancer Specialists, University of Nebraska Medical Center, Omaha, NE, USA;4. Eppley Institute for Cancer Research, University of Nebraska Medical Center, Omaha, NE, USA |
| 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. |
| Keywords: | Hormone-refractory prostate cancer Gemcitabine ErbB-2 inhibitor Combination therapy |
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