Inhibition of nicotinamide phosphoribosyltransferase and depletion of nicotinamide adenine dinucleotide contribute to arsenic trioxide suppression of oral squamous cell carcinoma.
Inhibition of nicotinamide phosphoribosyltransferase and depletion of nicotinamide adenine dinucleotide contribute to arsenic trioxide suppression of oral squamous cell carcinoma.
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抑制烟酰胺磷酸核糖基转移酶和消耗烟酰胺腺嘌呤二核苷酸有助于三氧化二砷抑制口腔鳞状细胞癌
DOI：
10.1016/j.taap.2017.05.008
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发表时间：
2017-09-15
影响因子：
3.8
通讯作者：
Xiang B
中科院分区：
文献类型：
--
作者：
Wang XY;Wang JZ;Gao L;Zhang FY;Wang Q;Liu KJ;Xiang B
新出现的证据表明，烟酰胺磷酸核糖转移酶（NAMPT）的表达增加与许多癌症的发展和预后有关，但它在口腔鳞状细胞癌（OSCC）中的作用仍然未知。在本研究中，组织芯片的结果表明，NAMPT在口腔鳞癌患者中过表达，其表达水平与肿瘤的分化程度直接相关。有趣的是，用化疗剂三氧化二砷（ATO）治疗OSCC细胞以ATO剂量和时间依赖性方式降低NAMPT蛋白水平并增加细胞死亡。最重要的是，低浓度ATO与FK866（NAMPT抑制剂）组合对NAMPT蛋白和mRNA表达产生增强的抑制作用，通过增加细胞凋亡和消耗细胞内烟酰胺腺嘌呤二核苷酸水平而导致对癌细胞的协同细胞毒性。这些发现表明NAMPT在OSCC预后中的关键作用，并揭示了抑制NAMPT作为ATO抑制癌细胞生长的新机制。本研究结果提示，ATO可显著增强NAMPT抑制剂的治疗效果，联合用药可能是治疗口腔鳞癌的一种新的有效策略。
Emerging evidence suggests that increased nicotinamide phosphoribosyltransferase (NAMPT) expression is associated with the development and prognosis of many cancers, but it remains unknown regarding its role in oral squamous cell carcinoma (OSCC). In the present study, the results from tissue microarray showed that NAMPT was overexpressed in OSCC patients and its expression level was directly correlated with differential grades of cancer. Interestingly, treatment of OSCC cells with chemotherapy agent arsenic trioxide (ATO) decreased the levels of NAMPT protein and increased cellular death in an ATO dose- and time-dependent manner. Most importantly, combination of low concentration ATO with FK866 (a NAMPT inhibitor) exerted enhanced inhibitive effect on NAMPT protein and mRNA expressions, leading to synergistic cytotoxicity on cancer cells through increasing cell apoptosis and depleting intracellular nicotinamide adenine dinucleotide levels. These findings demonstrate the crucial role of NAMPT in the prognosis of OSCC and reveal inhibition of NAMPT as a novel mechanism of ATO in suppressing cancer cell growth. Our results suggest that ATO can significantly enhance therapeutic efficacy of NAMPT inhibitor, and combined treatment may be a novel and effective therapeutic strategy for OSCC patients.
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影响因子：
4.8
作者：
Ding, Wei;Liu, Wenlan;Liu, Ke Jian
通讯作者：
Liu, Ke Jian
影响因子：
7.3
作者：
Galli, Ubaldina;Travelli, Cristina;Genazzani, Armando A.
通讯作者：
Genazzani, Armando A.
影响因子：
11.5
作者：
Gehrke, Iris;Bouchard, Eric D. J.;Banerji, Versha
通讯作者：
Banerji, Versha
影响因子：
3.5
作者：
Kitani, T;Okuno, S;Fujisawa, H
通讯作者：
Fujisawa, H
影响因子：
3.9
作者：
Roussel, RR;Barchowsky, A
通讯作者：
Barchowsky, A