Nitric Oxide (NO) is involved in many physiological and pathological processes. It is generated by a family of NO synthases (NOS), being the inducible isoform, iNOS, responsible for higher amounts of NO. Here, we report that pharmacological inhibition of NO production by l-NAME reduces both viability and MAPK activated signalling pathways in iNOS positive human and murine cancer cell lines. In vivo, using syngeneic models, in parallel with tumor reduction induced by l-NAME, collagen deposition and α-SMA positive stromal cells are observed. This observation takes place only when tumor cells express iNOS. In vitro, l-NAME induces viability and differentiation on fibroblast. Our results reveal that NO inhibition contributes to stimulate proliferation and activation of fibroblasts in parallel with tumor reduction of iNOS positive breast cancer.

中文翻译：

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N（G）-硝基-1-精氨酸甲酯（l-NAME）对乳腺肿瘤生长的抑制作用伴随着成纤维细胞的活化。

一氧化氮（NO）参与许多生理和病理过程。它是由一氧化氮合酶（NOS）家族产生的，NOS是可诱导的同工型，即iNOS，负责大量的NO。在这里，我们报告的药理学上抑制NO产生的l-NAME降低了iNOS阳性人和鼠癌细胞系的活力和MAPK激活的信号通路。在体内，使用同基因模型，与由l-NAME诱导的肿瘤减少同时，观察到胶原蛋白沉积和α-SMA阳性基质细胞。该观察仅在肿瘤细胞表达iNOS时发生。在体外，l-NAME诱导成纤维细胞的活力和分化。我们的结果表明，NO抑制与iNOS阳性乳腺癌的肿瘤减少同时，有助于刺激成纤维细胞的增殖和活化。