Caffeic acid phenethyl ester suppressed growth and metastasis of nasopharyngeal carcinoma cells by inactivating the NF-κB pathway
Caffeic acid phenethyl ester suppressed growth and metastasis of nasopharyngeal carcinoma cells by inactivating the NF-κB pathway
复制标题
咖啡酸苯乙酯通过灭活 NF-κ B 通路抑制鼻咽癌细胞的生长和转移
DOI：
10.2147/dddt.s199182
复制
发表时间：
2019-01-01
影响因子：
4.8
通讯作者：
Zhou, Xiaoying
中科院分区：
文献类型：
--
作者：
Liang, Yushan;Feng, Guofei;Zhou, Xiaoying
用途：咖啡酸苯乙酯（CAPE）是从蜂胶中提取的主要多酚，具有抑制多种肿瘤生长的作用。本研究旨在评估CAPE对鼻咽癌（NPC）的抑制作用，评估CAPE对鼻咽癌细胞系放疗敏感性的协同作用，并进一步阐明其可能的分子机制。 材料与方法：采用CCK-8法分析细胞增殖能力。集落形成试验用于评估CAPE处理后NPC细胞的克隆形成能力和放射敏感性。使用伤口愈合和跨孔测定来评估细胞的运动性。通过蛋白质印迹分析确定上皮-间质转化（EMT）关键分子的表达，并通过集落形成测定测量辐射敏感性的变化。 cDNA 微阵列分析用于确定经过和未经 CAPE 处理的差异表达基因，并确定基因功能和 KEGG 通路的基因本体富集。通过流式细胞术和蛋白质印迹分析检测细胞周期和细胞凋亡。结果：CAPE以时间和剂量依赖性方式抑制NPC细胞系的活力。它诱导 NPC 细胞凋亡，同时降低 Bcl-XL 的表达，增加 PARP 的裂解和 Bax 的表达。 CAPE 诱导 G1 期停滞，CDK4、CDK6、Rb 和 p-Rb 表达较低。 EMT途径降低了NPC细胞的迁移和侵袭能力。 CAPE 处理增强了 NPC 细胞的辐射敏感性。 CAPE 通过抑制 p65 亚基从细胞质到细胞核的易位来特异性抑制核因子 kappa B (NF-kappa B) 信号通路。 CAPE治疗与化疗和放疗具有协同作用。结论：CAPE可能通过抑制NF-κB通路抑制鼻咽癌细胞的增殖和转移，但增强鼻咽癌治疗的放射敏感性。 CAPE 可能是鼻咽癌治疗的潜在治疗化合物。
Purpose: Caffeic acid phenethyl ester (CAPE) is the main polyphenol extracted from honeybee propolis, which inhibits the growth of several kinds of tumor. This study aimed to assess the inhibitory effect of CAPE in nasopharyngeal carcinoma (NPC), evaluate the synergistic action of CAPE in radiotherapy sensitivity of NPC cell lines and further elucidate the possible molecular mechanism involved.Materials and methods: CCK-8 assay was used to analyze cell proliferation ability. Colony formation assay was used to evaluate the clonogenic ability and radio-sensitiveness of NPC cells by CAPE treatment. Wound-healing and transwell assay were used to assess the motility of cells. The expression of key molecules of the epithelial-mesenchymal transition (EMT) was determined by western blot analysis and changes in radiation sensitivity were measured by colony-formation assay. cDNA microarray analysis was used to determine differentially expressed genes with and without CAPE treatment, with Gene Ontology enrichment of gene function and KEGG pathways determined. Cell cycle and apoptosis were detected by flow cytometry and western blot analysis.Results: CAPE suppressed the viability of NPC cell lines time- and dose-dependently. It induced apoptosis in NPC cells along with decreased expression of Bcl-XL and increased cleavage of PARP and expression of Bax. G1 phase arrest was induced by CAPE with ower expression of CDK4, CDK6, Rb and p-Rb. The migratory and invasive ability of NPC cells was decreased by the EMT pathway. The irradiation sensitivity of NPC cells was enhanced with CAPE treatment. CAPE specifically inhibited nuclear factor kappa B (NF-kappa B) signaling pathway by suppressing p65 subunit translocation from cytoplasm to nucleus. CAPE treatment was synergistic with chemotherapy and radiotherapy.Conclusion: CAPE may inhibit the proliferation and metastasis of NPC cells but enhance radiosensitivity in NPC therapy by inhibiting the NF-kappa B pathway. CAPE could be a potential therapeutic compound for NPC therapy.