Capsaicin enhances cisplatin-induced anti-metastasis of nasopharyngeal carcinoma by inhibiting EMT and ERK signaling via serpin family B member 2.

IF 3.3 3区 医学 Q2 ONCOLOGY
Yafei Xu, Weimiao Kong, Simin Zhao, Dan Xiong, Yejun Wang
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引用次数: 0

Abstract

Cisplatin (DDP)-based combined chemotherapy or concurrent chemoradiotherapy is the mainstay treatment for advanced-stage nasopharyngeal carcinoma (NPC), but needs improvement due to its severe side effects. Capsaicin (CAP) can enhance the anti-tumor activity of cytotoxic drugs. The aim of this study was to investigate the anti-metastasis activity of CAP in combination with DDP in NPC. Herein, CAP and DDP showed synergistic cytotoxic effects on NPC cells. CAP alone and DDP alone inhibited NPC migration and invasion in vitro and in vivo, and the combination of CAP and DDP had the greatest effect. Moreover, CAP upregulated the mRNA and protein expressions of serpin family B member 2 (SERPINB2). Further results showed that both SERPINB2 mRNA and protein expressions were downregulated in NPC cell lines and tissues and SERPINB2 overexpression inhibited NPC migration and invasion in vitro and in vivo, while silencing SERPINB2 acted oppositely. In addition, SERPINB2 was abnormally expressed in head and neck squamous cell carcinoma and other multiple cancers, and downregulation of SERPINB2 predicted poor prognosis in head and neck squamous cell carcinoma according to the Cancer Genome Atlas database. We further found that SERPINB2 overexpression inhibited epithelial-mesenchymal transition (EMT) and the phosphorylated extracellular signal-regulated kinase (p-ERK), and the inhibitory effect was enhanced by CAP and DDP. Altogether, our results suggest that the combined inhibition of CAP and DDP on NPC metastasis may be related to the inhibition of epithelial-mesenchymal transition and ERK signals mediated by SERPINB2, and CAP may help to improve the efficacy of DDP in the treatment of NPC and develop new therapeutic approaches.

辣椒素通过SERPINB2抑制EMT和ERK信号转导,增强顺铂诱导的鼻咽癌抗转移能力
以顺铂(DDP)为基础的联合化疗或同期化放疗是治疗晚期鼻咽癌(NPC)的主要方法,但由于其严重的副作用而有待改进。辣椒素(CAP)可增强细胞毒性药物的抗肿瘤活性。本研究旨在探讨 CAP 联合 DDP 在鼻咽癌中的抗转移活性。在本研究中,CAP 和 DDP 对鼻咽癌细胞具有协同细胞毒性作用。单用CAP和单用DDP均可抑制鼻咽癌细胞在体外和体内的迁移和侵袭,而CAP和DDP联用的效果最好。此外,CAP还能上调SERPINB2的mRNA和蛋白表达。进一步的结果表明,SERPINB2 mRNA 和蛋白表达在鼻咽癌细胞系和组织中均出现下调,SERPINB2 的过表达抑制了鼻咽癌在体外和体内的迁移和侵袭,而沉默 SERPINB2 则起相反的作用。此外,SERPINB2 在头颈部鳞状细胞癌(HNSC)和其他多种癌症中异常表达,根据癌症基因组图谱(TCGA)数据库,SERPINB2 的下调预示着 HNSC 的不良预后。我们进一步发现,SERPINB2 的过表达可抑制上皮-间质转化(EMT)和磷酸化 ERK(p-ERK),CAP 和 DDP 可增强其抑制作用。总之,我们的研究结果表明,CAP和DDP联合抑制鼻咽癌转移可能与抑制SERPINB2介导的EMT和ERK信号有关,CAP可能有助于提高DDP治疗鼻咽癌的疗效并开发新的治疗方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Carcinogenesis
Carcinogenesis 医学-肿瘤学
CiteScore
9.20
自引率
2.10%
发文量
95
审稿时长
1 months
期刊介绍: Carcinogenesis: Integrative Cancer Research is a multi-disciplinary journal that brings together all the varied aspects of research that will ultimately lead to the prevention of cancer in man. The journal publishes papers that warrant prompt publication in the areas of Biology, Genetics and Epigenetics (including the processes of promotion, progression, signal transduction, apoptosis, genomic instability, growth factors, cell and molecular biology, mutation, DNA repair, genetics, etc.), Cancer Biomarkers and Molecular Epidemiology (including genetic predisposition to cancer, and epidemiology), Inflammation, Microenvironment and Prevention (including molecular dosimetry, chemoprevention, nutrition and cancer, etc.), and Carcinogenesis (including oncogenes and tumor suppressor genes in carcinogenesis, therapy resistance of solid tumors, cancer mouse models, apoptosis and senescence, novel therapeutic targets and cancer drugs).
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