当前位置: X-MOL 学术Theranostics › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Therapeutic potential of targeting MKK3-p38 axis with Capsaicin for Nasopharyngeal Carcinoma.
Theranostics ( IF 12.4 ) Pub Date : 2020-6-24 , DOI: 10.7150/thno.45191
Chengyao Chiang 1 , Min Zhang 1 , Dian Wang 2 , Tian Xiao 1 , Lizhi Zhu 3 , Kai Chen 4 , Junrong Huang 3 , Jingying Huang 1 , Jiang Zhu 1 , Li Li 1 , Cheng Chen 1 , Yangchao Chen 5 , Hongyi Hu 6 , Wenqi Jiang 7 , Yongdong Zou 1 , Ting Wang 2, 8 , Duo Zheng 1
Affiliation  

Background: Capsaicin is an active compound found in plants of the Capsicum genus; it has a range of therapeutic benefits, including anti-tumor effects. Here we aimed to delineate the inhibitory effects of capsaicin on nasopharyngeal carcinoma (NPC)./nMethods: The anti-cancer effects of capsaicin were confirmed in NPC cell lines and xenograft mouse models, using CCK-8, clonogenic, wound-healing, transwell migration and invasion assays. Co-immunoprecipitation, western blotting and pull-down assays were used to determine the effects of capsaicin on the MKK3-p38 axis. Cell proliferation and EMT marker expression were monitored in MKK3 knockdown (KD) or over-expression NPC cell lines treated with or without capsaicin. Finally, immunohistochemistry was performed on NPC specimens from NPC patients (n = 132) and the clinical relevance was analyzed./nResults: Capsaicin inhibited cell proliferation, mobility and promoted apoptosis in NPC cells. Then we found that capsaicin directly targets p38 for dephosphorylation. As such, MKK3-induced p38 activation was inhibited by capsaicin. Furthermore, we found that capsaicin-induced inhibition of cell motility was mediated by fucokinase. Xenograft models demonstrated the inhibitory effects of capsaicin treatment on NPC tumor growth in vivo, and analysis of clinical NPC samples confirmed that MKK3 phosphorylation was associated with NPC tumor growth and lymphoid node metastasis./nConclusions: The MKK3-p38 axis represents a potential therapeutic target for capsaicin. MKK3 phosphorylation might serve as a biomarker to identify NPC patients most likely to benefit from adjunctive capsaicin treatment.

中文翻译:

辣椒素靶向MKK3-p38轴对鼻咽癌的治疗潜力。

背景:辣椒素是在辣椒属植物中发现的一种活性化合物。它具有一系列治疗益处,包括抗肿瘤作用。在这里,我们的目的是勾画辣椒素对鼻咽癌(NPC)./ n的抑制作用方法:辣椒素的抗癌作用在NPC细胞系和异种移植小鼠模型中得到了证实,方法是使用CCK-8,克隆形成,伤口愈合,穿孔迁移和侵袭试验。使用共免疫沉淀,蛋白质印迹和下拉测定法确定辣椒素对MKK3-p38轴的作用。在用或不用辣椒素处理的MKK3敲低(KD)或过表达的NPC细胞系中监测细胞增殖和EMT标记的表达。最后,对来自NPC患者(n = 132)的NPC标本进行免疫组织化学,并分析其临床相关性辣椒素抑制NPC细胞的增殖,迁移并促进其凋亡。然后我们发现辣椒素直接靶向p38进行去磷酸化。因此,辣椒素抑制了MKK3诱导的p38活化。此外,我们发现辣椒素诱导的细胞运动抑制是由岩藻糖激酶介导的。异种移植模型证明了辣椒素治疗对体内NPC肿瘤生长具有抑制作用,临床NPC样品的分析证实MKK3磷酸化与NPC肿瘤生长和淋巴结转移有关。/n结论: MKK3-p38轴代表了潜在的治疗方法辣椒素的目标。MKK3磷酸化可能充当生物标志物,以鉴定最有可能从辅助辣椒素治疗中受益的NPC患者。
更新日期:2020-06-25
down
wechat
bug