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下调葡萄糖调节蛋白 78 可增强姜黄素对人鼻咽癌细胞的细胞毒性作用。

Downregulation of glucose-regulated protein 78 enhances the cytotoxic effects of curcumin on human nasopharyngeal carcinoma cells.

机构信息

Department of Ophthalmology, Shandong Provincial Third Hospital, Jinan, Shandong 250031, P.R. China.

Department of Ophthalmology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.

出版信息

Int J Mol Med. 2018 Nov;42(5):2943-2951. doi: 10.3892/ijmm.2018.3837. Epub 2018 Aug 23.

Abstract

Curcumin is a conventional Chinese medicine, which exerts a marked effect on various tumor types and suppresses tumor invasion. The present study analyzed the antineoplastic effects of curcumin on human nasopharyngeal carcinoma (NPC) cells and determined the effects of endoplasmic reticulum (ER) stress on curcumin‑induced cytotoxicity. The Cell Counting Kit‑8 assay examined the viability of SUNE1 and SUNE2 NPC cells. The Annexin V/propidium iodide staining technique was used to detect cell apoptosis and flow cytometry was used to examine cell cycle distribution. Western blotting and immunofluorescence were used to detect ER stress‑associated molecules. Furthermore, the toxic effects of curcumin treatment alongside glucose‑regulated protein 78 (GRP78) knockdown using small interfering (si)RNA, and treatment with the pan‑caspase inhibitor Z‑VAD‑FMK and the protein kinase B (AKT) inhibitor MK‑2206 were detected. The results demonstrated that curcumin markedly reduced cell viability, blocked cell cycle progression and induced apoptosis of human NPC cells. In addition, curcumin activated ER stress‑associated proteins to participate in the apoptosis of human NPC cells. siRNA‑induced knockdown of GRP78 may be able to strengthen the toxic effects of curcumin through mediating the AKT signaling pathway. These findings indicated that downregulation of GRP78 promoted the therapeutic effects of curcumin on NPC cells. The present study identified a potential, novel therapeutic method for the treatment of NPC.

摘要

姜黄素是一种传统中药,对多种肿瘤类型均具有显著作用,并能抑制肿瘤侵袭。本研究分析了姜黄素对人鼻咽癌细胞(NPC)的抗肿瘤作用,并确定内质网(ER)应激对姜黄素诱导的细胞毒性的影响。通过细胞计数试剂盒-8 检测 SUNE1 和 SUNE2 NPC 细胞的活力。采用 Annexin V/碘化丙啶染色技术检测细胞凋亡,采用流式细胞术检测细胞周期分布。采用 Western blot 和免疫荧光法检测 ER 应激相关分子。此外,还检测了姜黄素处理联合小干扰(si)RNA 敲低葡萄糖调节蛋白 78(GRP78)以及用泛半胱天冬酶抑制剂 Z-VAD-FMK 和蛋白激酶 B(AKT)抑制剂 MK-2206 处理的毒性作用。结果表明,姜黄素显著降低细胞活力,阻止细胞周期进程,并诱导人 NPC 细胞凋亡。此外,姜黄素激活 ER 应激相关蛋白参与人 NPC 细胞的凋亡。siRNA 诱导的 GRP78 敲低可能通过介导 AKT 信号通路增强姜黄素的毒性作用。这些发现表明下调 GRP78 促进了姜黄素对 NPC 细胞的治疗作用。本研究确定了一种治疗 NPC 的潜在新的治疗方法。

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