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Shuterin 通过 MAPK 和 Ras/Raf 信号通路上调颗粒酶 B 与 IFN-γ 表达水平增强自然杀伤白血病细胞系 KHYG-1 的细胞毒性

英文原题:Shuterin Enhances the Cytotoxicity of the Natural Killer Leukemia Cell Line KHYG-1 by Increasing the Expression Levels of Granzyme B and IFN-γ through the MAPK and Ras/Raf Signaling Pathways.

PubMed 2022/10/24(内容时间) Int J Mol Sci Q1 · IF 5.6(JCR 2025)

研究概要

自然杀伤(NK)细胞疗法是癌症免疫治疗的一种新兴工具。

中文摘要

自然杀伤(NK)细胞疗法是一种新兴的肿瘤免疫治疗工具。NK细胞从外周血中分离,其数量和活性有限。因此,原代NK细胞需要大幅扩增,并且必须增强其增殖和细胞毒性。Shuterin是一种从Ficus thonningii中分离的植物化学物质。在本研究中,我们探讨了shuterin增强KHYG-1细胞(一种NK白血病细胞系)增殖和活性的可能能力。Shuterin增强了KHYG-1细胞的增殖及其对K562细胞的细胞毒性。此外,该植物化学物质通过促进磷酸化环磷酸腺苷反应元件结合蛋白(CREB)和丝裂原活化蛋白激酶(MAPK)信号通路诱导颗粒酶B的表达。进一步地,随着KHYG-1细胞和来自头颈部鳞状细胞癌成人患者的NK细胞中shuterin水平的增加,干扰素(IFN)-的分泌也随之增加。Shuterin似乎通过增加凝集素样转录本1的表达以及Ras/Raf通路相关蛋白的磷酸化来诱导IFN-分泌。因此,shuterin是一种有前景的促进NK细胞增殖和细胞毒性的药物。

展开英文摘要原文

Natural killer (NK) cell therapy is an emerging tool for cancer immunotherapy. NK cells are isolated from peripheral blood, and their number and activity are limited. Therefore, primary NK cells should be expanded substantially, and their proliferation and cytotoxicity must be enhanced. Shuterin is a phytochemical isolated from Ficus thonningii . In this study, we explored the possible capacity of shuterin to enhance the proliferation and activity of KHYG-1 cells (an NK leukemia cell line). Shuterin enhanced the proliferation of KHYG-1 cells and their cytotoxicity to K562 cells. Moreover, this phytochemical induced the expression of granzyme B by promoting the phosphorylated cyclic adenosine monophosphate response element-binding protein (CREB) and mitogen-activated protein kinase (MAPK) signaling pathways. Furthermore, the secretion of interferon (IFN)- increased with increasing levels of shuterin in KHYG-1 cells and NK cells obtained from adults with head and neck squamous cell carcinoma. Shuterin appeared to induce IFN- secretion by increasing the expression of lectin-like transcript 1 and the phosphorylation of proteins involved in the Ras/Raf pathway. Thus, shuterin represents a promising agent for promoting the proliferation and cytotoxicity of NK cells.

论文信息

作者
Lin JT、Chuang YC、Chen MK、Lo YS、Lin CC、Ho HY、Liu YT、Hsieh MJ
第一作者单位
Department of Medicine, Division of Hematology and Oncology, Changhua Christian Hospital, Changhua 500, Taiwan.Taiwan
通讯作者单位
Oral Cancer Research Center, Changhua Christian Hospital, Changhua 500, Taiwan.Taiwan
期刊
International journal of molecular sciences2022 Oct 24
原文标识
PubMed 36361609 · DOI 10.3390/ijms232112816