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反式-维甲酰胺酸通过线粒体介导的凋亡途径抑制人鼻咽癌细胞的增殖并诱导其凋亡。

Trans-vaccenic acid inhibits proliferation and induces apoptosis of human nasopharyngeal carcinoma cells via a mitochondrial-mediated apoptosis pathway.

机构信息

Department of Otolaryngology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, 518035, People's Republic of China.

Institute of Translational Medicine, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, 518035, People's Republic of China.

出版信息

Lipids Health Dis. 2019 Feb 9;18(1):46. doi: 10.1186/s12944-019-0993-8.

Abstract

BACKGROUND

Intake of trans fatty acids (TFAs) from partially hydrogenated vegetable oil is associated with a variety of adverse outcomes, but little is known about the health effects of ruminant trans fats. Trans-vaccenic acid (TVA) is a naturally occurring TFA found in the fat of ruminants and in human dairy products. The present study was conducted to investigate the anticancer activity and underlying mechanisms of TVA on human nasopharyngeal carcinoma (NPC) 5-8F and CNE-2 cells.

METHODS

A CCK8 assay was used to determine the effect of TVA and the Mcl-1 inhibitor S63845 on the proliferation of NPC cells. Apoptosis was measured using flow cytometry. Western blotting was used to detect the protein expression levels of factors associated with Bcl-2-family protein signaling and Akt signaling.

RESULTS

TVA significantly inhibited cell proliferation in a dose-dependent manner. Mechanistic investigation demonstrated that TVA significantly decreased p-Akt levels and Bad phosphorylation on Ser-136 and Ser-112. More importantly, we discovered that the Mcl-1 inhibitor S63845 synergistically sensitized NPC cells to apoptosis induction by TVA.

CONCLUSION

TVA can inhibit NPC cell growth and induced apoptosis through the inhibition of Bad/Akt phosphorylation. The combined use of TVA and Mcl-1 inhibitors offers a potential advantage for nasopharyngeal cancer treatment.

摘要

背景

部分氢化植物油中的反式脂肪酸(TFAs)的摄入与多种不良后果有关,但关于反刍动物反式脂肪的健康影响知之甚少。反式- Vaccenic 酸(TVA)是一种天然存在的 TFA,存在于反刍动物的脂肪和人类乳制品中。本研究旨在探讨 TVA 对人鼻咽癌(NPC)5-8F 和 CNE-2 细胞的抗癌活性及其潜在机制。

方法

用 CCK8 法测定 TVA 和 Mcl-1 抑制剂 S63845 对 NPC 细胞增殖的影响。用流式细胞术检测细胞凋亡。Western blot 检测与 Bcl-2 家族蛋白信号和 Akt 信号相关的因子的蛋白表达水平。

结果

TVA 呈剂量依赖性显著抑制细胞增殖。机制研究表明,TVA 显著降低了 p-Akt 水平和 Bad 在 Ser-136 和 Ser-112 上的磷酸化。更重要的是,我们发现 Mcl-1 抑制剂 S63845 可协同增强 TVA 诱导 NPC 细胞凋亡的敏感性。

结论

TVA 可通过抑制 Bad/Akt 磷酸化抑制 NPC 细胞生长并诱导细胞凋亡。TVA 和 Mcl-1 抑制剂的联合使用为鼻咽癌的治疗提供了潜在的优势。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8115/6368753/5a3537f9a3f5/12944_2019_993_Fig1_HTML.jpg

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