期刊
CLINICAL CANCER RESEARCH
卷 20, 期 10, 页码 2663-2673出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-13-2305
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类别
资金
- Association pour le Developpement de l'Hemato-Oncologie (ADHO)
- Ligue contre le cancer
- INSERM
- Region Bretagne
- Universite de Rennes 1
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 antitumor 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 cocultured or cultured alone with celecoxib treatment, a nonsteroidal anti-inflammatory drug, and/or TRAIL, a promising cytotoxic molecule for cancer therapy. Results: In this study, we show that follicular lymphoma stromal cells produce large amounts of PGE(2). This production is abrogated after celecoxib treatment, targeting the COX-2 isoenzyme involved in PGE(2) synthesis. Furthermore, we demonstrate that celecoxib increases apoptosis in NHL B-cell lines and in primary follicular lymphoma B cells cocultured with stromal cells, but independently of the PGE(2)/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 tumor B cells and survival signals provided by the tumor microenvironment. (C) 2014 AACR.
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