Apoptosis-based treatment of glioblastomas with ABT-737, a novel small molecule inhibitor of Bcl-2 family proteins.
作者： K E Tagscherer , A Fassl , B Campos , M Farhadi , A Kraemer
DOI: 10.1038/ONC.2008.259
关键词:
摘要: Defects in the apoptotic signaling cascades contribute to poor therapeutic response of malignant gliomas. As glioblastomas are characterized by high expression levels anti-apoptotic Bcl-2 family proteins, we studied effects novel inhibitor, ABT-737, on glioma cells. ABT-737 treatment released pro-apoptotic Bax protein from its binding partner and potently induced cell death glioblastoma cells vitro vivo. The local administration prolonged survival an intracranial xenograft model. Downregulation Mcl-1 overexpression sensitized ABT-737-mediated apoptosis. Moreover, potentiated cytotoxicity chemotherapeutic drugs vincristine etoposide, ligand TRAIL. stem may play a crucial role for tumor progression resistance glioblastomas, investigated subpopulation exhibiting characteristics. Inhibition proliferation induction apoptosis were less efficient than non-stem cell-like was associated with levels, combined downregulation could represent promising approach treatment.
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nature.com参考文章(53)
Jürgen A. Kraus, Matthias Wenghoefer, Nicole Glesmann, Svenja Mohr, Martina Beck, Matthias C. Schmidt, Rolf Schröder, Ute Berweiler, Wolfgang Roggendorf, Sabine Diete, Knut Dietzmann, Karlheinz Heuser, Bettina Müller, Rolf Fimmers, Andreas von Deimling, Uwe Schlegel, TP53 gene mutations, nuclear p53 accumulation, expression of Waf/p21, Bcl-2, and CD95 (APO-1/Fas) proteins are not prognostic factors in de novo glioblastoma multiforme. Journal of Neuro-oncology. ,vol. 52, pp. 263- 272 ,(2001) , 10.1023/A:1010684203704
B. Lach, S. Krajewski, M. Sikorska, J. Ehrmann, J. C. Reed, J. Chatten, M. Krajewska, Immunohistochemical analysis of Bcl-2, Bcl-X, Mcl-1, and Bax in tumors of central and peripheral nervous system origin. American Journal of Pathology. ,vol. 150, pp. 805- 814 ,(1997)
R Gascoyne, A Shabaik, S Krajewski, J C Reed, S Bodrug, M Krajewska, K Berean, Immunohistochemical analysis of Mcl-1 protein in human tissues. Differential regulation of Mcl-1 and Bcl-2 protein production suggests a unique role for Mcl-1 in control of programmed cell death in vivo. American Journal of Pathology. ,vol. 146, pp. 1309- 1319 ,(1995)
Avi Ashkenazi, Ian F. Pollack, Melanie Erff, Direct Stimulation of Apoptotic Signaling by Soluble Apo2L/Tumor Necrosis Factor-related Apoptosis-inducing Ligand Leads to Selective Killing of Glioma Cells Clinical Cancer Research. ,vol. 7, pp. 1362- 1369 ,(2001)
S. Huang, F. A. Sinicrope, BH3 mimetic ABT-737 potentiates TRAIL-mediated apoptotic signaling by unsequestering Bim and Bak in human pancreatic cancer cells. Cancer Research. ,vol. 68, pp. 2944- 2951 ,(2008) , 10.1158/0008-5472.CAN-07-2508
UWE ZANGEMEISTER-WITTKE, Antisense to Apoptosis Inhibitors Facilitates Chemotherapy and TRAIL‐Induced Death Signaling Annals of the New York Academy of Sciences. ,vol. 1002, pp. 90- 94 ,(2003) , 10.1196/ANNALS.1281.019
A Eramo, L Ricci-Vitiani, A Zeuner, R Pallini, F Lotti, G Sette, E Pilozzi, L M Larocca, C Peschle, R De Maria, Chemotherapy resistance of glioblastoma stem cells Cell Death & Differentiation. ,vol. 13, pp. 1238- 1241 ,(2006) , 10.1038/SJ.CDD.4401872
Rezvan Ahmadi, Sabine Urig, Marius Hartmann, Burkhard M. Helmke, Sasa Koncarevic, Bianca Allenberger, Christine Kienhoefer, Markus Neher, Hans-Herbert Steiner, Andreas Unterberg, Christel Herold-Mende, Katja Becker, Antiglioma activity of 2,2′:6′,2ʺ-terpyridineplatinum(II) complexes in a rat model—Effects on cellular redox metabolism Free Radical Biology and Medicine. ,vol. 40, pp. 763- 778 ,(2006) , 10.1016/J.FREERADBIOMED.2005.09.031
R.J. Gillies, N. Didier, M. Denton, Determination of cell number in monolayer cultures Analytical Biochemistry. ,vol. 159, pp. 109- 113 ,(1986) , 10.1016/0003-2697(86)90314-3
Sibylle Karcher, Hans-Herbert Steiner, Rezvan Ahmadi, Saida Zoubaa, Gergely Vasvari, Harry Bauer, Andreas Unterberg, Christel Herold-Mende, Different angiogenic phenotypes in primary and secondary glioblastomas. International Journal of Cancer. ,vol. 118, pp. 2182- 2189 ,(2006) , 10.1002/IJC.21648