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COX-2 independent effects of Celecoxib sensitize Lymphoma B cells to TRAIL-mediated apoptosis.

Abstract : PURPOSE: Despite therapeutic advances, Non-Hodgkin lymphomas (NHL) remain incurable. They form a group of neoplasms strongly dependent on their inflammatory microenvironment, which plays an important supportive role in tumor B-cell survival and in the resistance to anti-tumor immune response. New therapies must consider both tumor cells and their surrounding microenvironment EXPERIMENTAL DESIGN: Stromal cells, derived from bone marrow or lymph nodes, and B cells from follicular lymphoma patients were co-cultured or cultured alone with Celecoxib treatment, a non-steroidal anti-inflammatory drug and/or TRAIL, a promising cytotoxic molecule for cancer therapy. RESULTS: In this study, we show that follicular lymphoma (FL) stromal cells produce large amounts of PGE2. This production is abrogated after Celecoxib treatment, targeting the COX-2 isoenzyme involved in PGE2 synthesis. Furthermore, we demonstrate that Celecoxib increases apoptosis in NHL B-cell lines and in primary FL B-cells co-cultured with stromal cells, but independently of the PGE2/COX-2 axis. Finally, Celecoxib increases the apoptotic activity of TRAIL. We provide evidence that Celecoxib affects proliferation and sensitizes NHL B-cell lines to apoptosis through COX-2 independent effects by slowing down the cell cycle and decreasing the expression of survival proteins, such as Mcl-1. CONCLUSIONS: These data suggest new potent strategies for NHL therapy combining drugs targeting both tumour B cells and survival signals provided by the tumor microenvironment.
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https://hal-univ-rennes1.archives-ouvertes.fr/hal-00974518
Contributor : Laurent Jonchère <>
Submitted on : Monday, April 7, 2014 - 10:17:07 AM
Last modification on : Thursday, June 11, 2020 - 3:19:19 AM

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Anne-Sophie Gallouët, Marion Travert, Laurence Bresson-Bepoldin, Fabien Guilloton, Celine Pangault, et al.. COX-2 independent effects of Celecoxib sensitize Lymphoma B cells to TRAIL-mediated apoptosis.. Clinical Cancer Research, American Association for Cancer Research, 2014, 20 (10), pp.2663-73. ⟨10.1158/1078-0432.CCR-13-2305⟩. ⟨hal-00974518⟩

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