NF-κB–independent down-regulation of XIAP by bortezomib sensitizes HL B cells against cytotoxic drugs

作者: Hamid Kashkar , Anke Deggerich , Jens-Michael Seeger , Benjamin Yazdanpanah , Katja Wiegmann

DOI: 10.1182/BLOOD-2006-10-053959

关键词: Cancer researchProteasome inhibitorDownregulation and upregulationNF-κBXIAPCytotoxicityBiologyBortezomibCytotoxic T cellCell culture

摘要: The proteasome inhibitor bortezomib has been shown to possess promising antitumor activity and significant efficacy against a variety of malignancies. Different studies demonstrated that breaks the chemoresistance in different tumor cells basically by altering nuclear factor–κB (NF-κB) activity. NF-κB be constitutively active most primary Hodgkin-Reed-Sternberg (H-RS) lymph node sections Hodgkin lymphoma (HL) cell lines was suggested central molecular switch apoptosis resistance HL. Here we report bimodal effect HL cells. Whereas high-dose induced direct cytotoxicity correlated with decreased activity, low-dose sensitized cytotoxic drugs without action. Strikingly, marked XIAP down-regulation at posttranslational level independent status. Similarly, RNA interference (RNAi)–mediated generated susceptibility cytostatic agents. results identify as an NF-κB–independent target action controls chemoresistant phenotype

参考文章(40)
RC Bargou, C Leng, D Krappmann, F Emmerich, MY Mapara, K Bommert, HD Royer, C Scheidereit, B Dorken, High-level nuclear NF-kappa B and Oct-2 is a common feature of cultured Hodgkin/Reed-Sternberg cells Blood. ,vol. 87, pp. 4340- 4347 ,(1996) , 10.1182/BLOOD.V87.10.4340.BLOODJOURNAL87104340
Martin Holcik, Charles Lefebvre, Chiaoli Yeh, Terry Chow, Robert G. Korneluk, A new internal-ribosome-entry-site motif potentiates XIAP- mediated cytoprotection Nature Cell Biology. ,vol. 1, pp. 190- 192 ,(1999) , 10.1038/11109
Theresa Marafioti, Michael Hummel, Hans-Dieter Foss, Helmut Laumen, Petra Korbjuhn, Ioannis Anagnostopoulos, Hetty Lammert, Gudrun Demel, Jan Theil, Thomas Wirth, Harald Stein, Hodgkin and Reed-Sternberg cells represent an expansion of a single clone originating from a germinal center B-cell with functional immunoglobulin gene rearrangements but defective immunoglobulin transcription Blood. ,vol. 95, pp. 1443- 1450 ,(2000) , 10.1182/BLOOD.V95.4.1443.004K55_1443_1450
Volkhard Seitz, Michael Hummel, Theresa Marafioti, Ioannis Anagnostopoulos, Chalid Assaf, Harald Stein, Detection of clonal T-cell receptor gamma-chain gene rearrangements in Reed-Sternberg cells of classic Hodgkin disease Blood. ,vol. 95, pp. 3020- 3024 ,(2000) , 10.1182/BLOOD.V95.10.3020
Shan Man, Peter Elliott, Robert S. Kerbel, Julian Adams, Andrea Frankel, Lack of multicellular drug resistance observed in human ovarian and prostate carcinoma treated with the proteasome inhibitor PS-341. Clinical Cancer Research. ,vol. 6, pp. 3719- 3728 ,(2000)
Rihab Nasr, Marwan E El-Sabban, José-Antonio Karam, Ghassan Dbaibo, Youmna Kfoury, Bertrand Arnulf, Yves Lepelletier, Françoise Bex, Hugues de Thé, Olivier Hermine, Ali Bazarbachi, Efficacy and mechanism of action of the proteasome inhibitor PS-341 in T-cell lymphomas and HTLV-I associated adult T-cell leukemia/lymphoma Oncogene. ,vol. 24, pp. 419- 430 ,(2005) , 10.1038/SJ.ONC.1208212
GM Cohen, JB Almond, The proteasome: a novel target for cancer chemotherapy. Leukemia. ,vol. 16, pp. 433- 443 ,(2002) , 10.1038/SJ.LEU.2402417
Daniel Re, Andreas Hofmann, Jürgen Wolf, Volker Diehl, Andrea Staratschek-Jox, Cultivated H-RS cells are resistant to CD95L-mediated apoptosis despite expression of wild-type CD95. Experimental Hematology. ,vol. 28, pp. 31- 35 ,(2000) , 10.1016/S0301-472X(99)00125-3