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附子治疗对荷H22肿瘤小鼠通过调节适应性免疫和自然杀伤相关免疫的免疫调节作用

The Immunoregulatory Effect of Aconite Treatment on H22 Tumor-Bearing Mice via Modulating Adaptive Immunity and Natural Killer-Related Immunity.

作者信息

Wang Huan, Qi Xiu Zhong, Jia Wentao, Yu Jiahui, Yang Kangdi, Zhang Xu, Wang Lina

机构信息

Department of Traditional Chinese Medicine, Naval Medical University, No. 168 Changhai Road, Shanghai 200433, China.

Unit 71345 of the Chinese People's Liberation Army, Zibo 255000, China.

出版信息

Evid Based Complement Alternat Med. 2023 Jan 30;2023:1481114. doi: 10.1155/2023/1481114. eCollection 2023.

DOI:10.1155/2023/1481114
PMID:36756040
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9902160/
Abstract

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and, in its advanced stages, has a 5-year survival rate of only 3% to 5%. Despite novel mechanisms and treatments being uncovered over the past few years, effective strategies for HCC are currently limited. Previous studies have proven that aconite can suppress tumor growth and progression and prevent the recurrence and metastasis of multiple cancers, but the underlying molecular mechanisms are largely unknown. In this study, different doses of aconite were applied to mice bearing subcutaneous HCC tumors. It was found that aconite had a therapeutic effect on H22 tumor-bearing mice in a dose-dependent manner by reducing tumor volumes and prolonging survival times, which could be attributed to the immunoregulatory effect of aconite. Furthermore, results showed that high-dose administration of aconite could enhance adaptive immunity and natural killer (NK) cell-mediated immunity by regulating the secretion of interferon-, upregulating T cells and NK cells, and modulating the expression of the NK cytotoxicity biomarker CD107a and the inhibitory receptor TIGIT. This study revealed a novel mechanism through which aconite exerts antitumor effects, not merely through apoptosis induction pathways, providing more sound evidence that aconite has the potential to be developed into an effective anti-HCC agent.

摘要

肝细胞癌(HCC)是原发性肝癌最常见的类型,在晚期阶段,其5年生存率仅为3%至5%。尽管在过去几年中发现了新的机制和治疗方法,但目前针对HCC的有效策略仍然有限。先前的研究已经证明附子可以抑制肿瘤生长和进展,并预防多种癌症的复发和转移,但其潜在的分子机制在很大程度上尚不清楚。在本研究中,将不同剂量的附子应用于皮下接种HCC肿瘤的小鼠。结果发现,附子通过减小肿瘤体积和延长生存时间,对荷H22肿瘤小鼠具有剂量依赖性的治疗作用,这可能归因于附子的免疫调节作用。此外,结果表明,高剂量的附子给药可以通过调节干扰素-的分泌、上调T细胞和NK细胞以及调节NK细胞毒性生物标志物CD107a和抑制性受体TIGIT的表达,增强适应性免疫和自然杀伤(NK)细胞介导的免疫。本研究揭示了附子发挥抗肿瘤作用的一种新机制,而不仅仅是通过细胞凋亡诱导途径,为附子有潜力被开发成一种有效的抗HCC药物提供了更有力的证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dc5/9902160/0a3f3ed9a41b/ECAM2023-1481114.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dc5/9902160/7919dcc2d0bc/ECAM2023-1481114.001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dc5/9902160/7919dcc2d0bc/ECAM2023-1481114.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dc5/9902160/c3e6e369bd69/ECAM2023-1481114.002.jpg
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TNF-α-dependent lung inflammation upregulates PD-L1 in monocyte-derived macrophages to contribute to lung tumorigenesis.肿瘤坏死因子-α依赖的肺部炎症会上调单核细胞衍生巨噬细胞中的程序性死亡受体配体1,从而促进肺部肿瘤发生。
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