Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen University International Cancer Center, Department of Cell Biology and Genetics, School of Medicine, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518055, China.
Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410013, China.
Theranostics. 2020 Jun 24;10(17):7906-7920. doi: 10.7150/thno.45191. eCollection 2020.
Capsaicin is an active compound found in plants of the 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). 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. 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 , and analysis of clinical NPC samples confirmed that MKK3 phosphorylation was associated with NPC tumor growth and lymphoid node metastasis. 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.
辣椒素是辣椒属植物中的一种活性化合物，具有多种治疗益处，包括抗肿瘤作用。在这里，我们旨在描述辣椒素对鼻咽癌（NPC）的抑制作用。通过 CCK-8、集落形成、划痕愈合、Transwell 迁移和侵袭测定，在 NPC 细胞系和异种移植小鼠模型中证实了辣椒素的抗癌作用。用 co-immunoprecipitation、western blotting 和 pull-down 测定来确定辣椒素对 MKK3-p38 轴的影响。在用或不用辣椒素处理的 MKK3 敲低（KD）或过表达 NPC 细胞系中监测细胞增殖和 EMT 标志物表达。最后，对来自 NPC 患者的 NPC 标本进行免疫组化分析，并分析其临床相关性（n=132）。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使 p38 去磷酸化。因此，MKK3 诱导的 p38 激活被辣椒素抑制。此外，我们发现辣椒素诱导的细胞迁移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 NPC 肿瘤生长的抑制作用，对临床 NPC 样本的分析证实了 MKK3 磷酸化与 NPC 肿瘤生长和淋巴结转移有关。MKK3-p38 轴是辣椒素的一个潜在治疗靶点。MKK3 磷酸化可能作为一个生物标志物，用于识别最有可能从辅助辣椒素治疗中获益的 NPC 患者。
