Grimm Elizabeth A, Ellerhorst Julie, Tang Chi-Hui, Ekmekcioglu Suhendan
Department of Experimental Therapeutics, University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Nitric Oxide. 2008 Sep;19(2):133-7. doi: 10.1016/j.niox.2008.04.009. Epub 2008 Apr 22.
Human melanoma tumors cells are known to express the enzyme, inducible nitric oxide synthase (iNOS), which is responsible for cytokine induced nitric oxide (NO) production during immune responses. This constitutive expression of iNOS in many patients' tumor cells, as well as its strong association with poor patient survival, have led to the consideration of iNOS as a molecular marker of poor prognosis, as well as a possible target for therapy. The expression of iNOS in patient tumors was found to associate with nitrotyrosine, COX2, pSTAT3, and arginase. Using human melanoma patients' samples as well as cell lines, we have further evidence supporting intracellular NO production by detection of nitrotyrosine and also by use of DAF-2DA staining. Experiments were performed to scavenge the endogenous NO (with c-PTIO) resulting in melanoma cell growth inhibition; this was restored with SIN-1 (NO and O2-donor) providing data to support a functional role of this gas. Our goal is to understand the aberrant biology leading to this curious phenomenon, and to regulate it in favor of patient treatments.
已知人类黑色素瘤肿瘤细胞会表达诱导型一氧化氮合酶（iNOS），该酶在免疫反应期间负责细胞因子诱导的一氧化氮（NO）生成。iNOS在许多患者肿瘤细胞中的这种组成性表达，以及它与患者不良生存的强烈关联，已导致人们将iNOS视为预后不良的分子标志物以及可能的治疗靶点。研究发现，患者肿瘤中iNOS的表达与硝基酪氨酸、COX2、pSTAT3和精氨酸酶相关。利用人类黑色素瘤患者的样本以及细胞系，我们通过检测硝基酪氨酸以及使用DAF-2DA染色，获得了支持细胞内NO生成的进一步证据。进行实验以清除内源性NO（使用c-PTIO），结果导致黑色素瘤细胞生长受到抑制；使用SIN-1（NO和O2供体）可恢复这种生长抑制，这为支持这种气体的功能作用提供了数据。我们的目标是了解导致这种奇特现象的异常生物学机制，并对其进行调节以利于患者治疗。
