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Lymphoma and myeloma cell resistance to cytotoxic agents and ionizing radiations is not affected by exposure to anti-IL-6 antibody: IL-6 and resistance to cytotoxics

Abstract : Background: Production of high levels of IL-6 is often correlated with resistance to cytotoxics or ionizing radiations, in cancer cell lines as in various cancer patients. We investigated whether monoclonal antibodies directed against IL-6 may enable to reverse resistance of cancer cell lines. Methodology/Principal Findings: We exposed ten haematological cancer cells from lymphoma, myeloma or leukemia origins to cytotoxics or ionizing radiations and assessed the effects of anti-IL-6 antibody addition on cell proliferation, apoptosis or IL-6 signaling. A strong correlation between IL-6 secretion, measured by ELISA, and resistance to doxorubicin as ionizing radiations was observed in the multiple myeloma U266 and the Burkitt's lymphoma Daudi and Namalwa cells. Although an anti-IL-6 antibody combined to both treatments efficiently blocked IL-6 signaling in U266 cells, expressing the IL-6 receptor gp80, it did not increase treatment-induced anti-proliferative and pro-apoptotic effects on these cells, as well as on Daudi and Namalwa cells. This lack of effect could be related to diverse factors: 1) a higher release of the soluble form of IL-6 receptor gp80 in response to doxorubicin and irradiation from all cell lines, 2) an impaired level of the IL-6 pathway inhibitor SOCS3 in Daudi cells, and 3) an increased release of IL-10 and TNFα, two cytokines involved in cell radio- and chemoresistance. Conclusions/significance: These data support the fact that IL-6 is not the preponderant actor of cell resistance to cytotoxics and ionizing radiations, which seems to be regulated by a complex network of proteins.
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https://www.hal.inserm.fr/inserm-00441337
Contributor : Angélique Gougelet Connect in order to contact the contributor
Submitted on : Tuesday, December 15, 2009 - 4:57:59 PM
Last modification on : Thursday, November 21, 2019 - 2:30:20 AM
Long-term archiving on: : Thursday, June 17, 2010 - 9:50:20 PM

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  • HAL Id : inserm-00441337, version 1
  • PUBMED : 19956602

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Angélique Gougelet, Adeline Mansuy, Jean-yves Blay, Laurent Alberti, Claudine Vermot-Desroches. Lymphoma and myeloma cell resistance to cytotoxic agents and ionizing radiations is not affected by exposure to anti-IL-6 antibody: IL-6 and resistance to cytotoxics. PLoS ONE, Public Library of Science, 2009, http://dx.plos.org/10.1371/journal.pone.0008026. ⟨inserm-00441337⟩

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