Nitrogen Containing Bisphosphonates Induce Apoptosis and Inhibit the Mevalonate Pathway, Impairing Ras Membrane Localization in Prostate Cancer Cells
作者： GRENVILLE M. OADES , SIDDHIKA G. SENARATNE , IAN A. CLARKE , ROGER S. KIRBY , KAY W. COLSTON
DOI: 10.1097/01.JU.0000070685.34760.5F
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摘要: ABSTRACTPurpose: Metastasis to bone is an important cause of morbidity in advanced prostate cancer. Despite the typically sclerotic nature prostatic metastases osteolysis has a significant role pathogenesis this disease. The nitrogen containing bisphosphonates (N-BPs), such as pamidronate and zoledronic acid, have greatly enhanced potency for inhibiting resorption inducing apoptosis osteoclasts. We investigated effects N-BPs on cancer cells.Materials Methods: Cell viability was determined with MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymeyhoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) dye reduction assay. cycle analysis, DNA fragmentation caspase 3 activity were assessed using flow cytometry. Ras, Bcl-2 Bax quantified by Western blotting.Results: Pamidronate acid decreased cell human lines DU145, PC3 LNCaP. These associated changes distribution, induction D...
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