tailieunhanh - Báo cáo khoa học: "The Akt-inhibitor Erufosine induces apoptotic cell death in prostate cancer cells and increases the short term effects of ionizing radiation"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Radiation Oncology cung cấp cho các bạn kiến thức về ngành y đề tài: The Akt-inhibitor Erufosine induces apoptotic cell death in prostate cancer cells and increases the short term effects of ionizing radiation. | Rudner et al. Radiation Oncology 2010 5 108 http content 5 1 108 RADIATION ONCOLOGY RESEARCH Open Access The Akt-inhibitor Erufosine induces apoptotic cell death in prostate cancer cells and increases the short term effects of ionizing radiation 1 1 4 5 Justine Rudner Carola-Ellen Ruiner René Handrick Hans-Jorg Eibl Claus Belka Verena Jendrossek 1 Abstract Background and Purpose The phosphatidylinositol-3-kinase PI3K Akt pathway is frequently deregulated in prostate cancer and associated with neoplastic transformation malignant progression and enhanced resistance to classical chemotherapy and radiotherapy. Thus it is a promising target for therapeutic intervention. In the present study the cytotoxic action of the Akt inhibitor Erufosine ErPC3 was analyzed in prostate cancer cells and compared to the cytotoxicity of the PI3K inhibitor LY294002. Moreover the efficacy of combined treatment with Akt inhibitors and ionizing radiation in prostate cancer cells was examined. Materials and methods Prostate cancer cell lines PC3 DU145 and LNCaP were treated with ErPC3 1-100 pM LY294002 25-100 pM irradiated 0-10 Gy or subjected to combined treatments. Cell viability was determined by the WST-1 assay. Apoptosis induction was analyzed by flow cytometry after staining with propidium iodide in a hypotonic citrate buffer and by Western blotting using antibodies against caspase-3 and its substrate PARP. Akt activity and regulation of the expression of Bcl-2 family members and key downstream effectors involved in apoptosis regulation were examined by Western blot analysis. Results The Akt inhibitor ErPC3 exerted anti-neoplastic effects in prostate cancer cells however with different potency. The anti-neoplastic action of ErPC3 was associated with reduced phosphoserine 473-Akt levels and induction of apoptosis. PC3 and LNCaP prostate cancer cells were also sensitive to treatment with the PI3K inhibitor LY294002. However the ErPC3-sensitive PC3-cells were .

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