TNFα antagonization alters NOS2 dependent nasopharyngeal carcinoma tumor growth

被引:10
作者
Bourouba, Mehdi [1 ,4 ]
Zergoun, Ahmed-Amine [1 ]
Maffei, Joseph S. [4 ]
Chila, Dalia [2 ]
Djennaoui, Djamel [3 ]
Asselah, Fatima [2 ]
Amir-Tidadini, Zine-Charef [2 ]
Touil-Boukoffa, Chafia [1 ]
Zaman, Muhammad H. [4 ]
机构
[1] Univ Houari Boumediene USTHB, Fac Biol, Team Cytokines & Nitr Oxide Synth, Dept Cell & Mol Biol, Algiers, Algeria
[2] Mustapha Pacha Hosp, Cent Lab Anatomopathol, Algiers, Algeria
[3] Mustapha Pacha Hosp, Dept Otorhinolaryngol, Algiers, Algeria
[4] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA
关键词
NPC; Nitric oxide; Tumor; TNF alpha; Proliferation; NITRIC-OXIDE SYNTHASE; NECROSIS-FACTOR-ALPHA; T-LYMPHOCYTES; DNA-DAMAGE; INFLAMMATION; ACTIVATION; EXPRESSION; BCL-2; ACCUMULATION; ANGIOGENESIS;
D O I
10.1016/j.cyto.2015.04.003
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Tumor necrosis factor (TNF alpha) is a pro-inflammatory cytokine which mediates via nitric oxide (NO) several carcinogenic processes. Increasing evidences suggest that NO promotes inflammation induced growth of nasopharyngeal carcinoma (NPC). In patients, TNF alpha synthesis associates with poor survival. To explore the effect of the cytokine on NO production and NOS2 dependent NPC growth, NO2- (nitrite) producing cells in patients were analyzed in vitro. We observed that patients' monocytes/macrophages (Mo/Ma) and primary tumor biopsies synthesized significant amounts of NO2-. Interestingly, tumor explants derived NO2- levels were more important in elderly patients in comparison with juveniles. Endogenous TNF alpha neutralization with an anti-TNF alpha monoclonal antibody (mAb) successfully inhibited NO2- synthesis by blood mononuclear cells and tumor explants. Recombinant TNF alpha (rTNF alpha) enhanced NO2- synthesis and C666-1 NPC cell proliferation. NOS2 selective inhibition (1400W) and TNF alpha antagonization with an anti-TNFa mAb potently inhibited rTNF alpha induced C666-1 proliferation and NOT production. Importantly, primary tumors treated with the anti-TNF alpha mAb also displayed reduced proliferation index (Ki67). Altogether, our results define monocytes/macrophages and the primary tumor as major sources of circulating NO2- in NPC patients and support the idea that antibody dependent inhibition of the TNF alpha/NOS2 pathway may alter NPC tumor growth. (C) 2015 Elsevier Ltd. All rights reserved.
引用
收藏
页码:157 / 163
页数:7
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