研究动态
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紫河车素盐酸盐通过调节AMPK途径,双向抑制肿瘤和自身免疫性疾病的发展。

Sinomenine hydrochloride bidirectionally inhibits progression of tumor and autoimmune diseases by regulating AMPK pathway.

发表日期:2023 Mar 09
作者: Run Ze Li, Xiao Xiang Guan, Xuan Run Wang, Wei-Qian Bao, Li-Rong Lian, Seong Wang Choi, Fang Yuan Zhang, Pei-Yu Yan, Elaine Lai Han Leung, Hu-Dan Pan, Liang Liu
来源: CYTOKINE & GROWTH FACTOR REVIEWS

摘要:

慢性疾病如肿瘤和自身免疫性疾病与新陈代谢和免疫密切相关,并需要相互冲突的治疗方法。AMPK可以通过能量代谢调节细胞生长和炎症。青黛是一种从中药草青藤(Thunb。)提取的化合物Rehd。et Wils.已经在一些研究中用于治疗非小细胞肺癌(NSCLC)和类风湿性关节炎(RA),但对其机制的了解有限。本研究旨在研究青黛氢氯酸盐(SH)对NSCLC和RA的抑制作用,并了解其潜在联合机制。结果表明,SH具有肿瘤细胞细胞毒作用,但对正常细胞没有作用。SH被发现通过激活AMPK-mTOR通路诱导细胞凋亡。此外,在自身免疫疾病细胞模型中,SH通过抑制AMPK磷酸化来减少RA-FLS细胞的生长,但对正常巨噬细胞没有影响。此外,体内研究还表明,SH可以减少大鼠辅助性关节炎中的促炎细胞因子TNF-α,IL-1β和IL-6的产生并减缓大鼠关节炎的发展。此外,SH还被发现在小鼠肿瘤异种移植实验中显着抑制肿瘤生长。本研究通过展示SH可以通过激活AMPK通路选择性地抑制NSCLC细胞的生长和RA的进展,为治疗肿瘤和自身免疫疾病提供了新的见解。版权所有©2023 Elsevier GmbH。保留所有权利。
Chronic diseases such as tumors and autoimmune disorders are closely linked to metabolism and immunity and require conflicting treatment methods. AMPK can regulate cell growth and inflammation through energy metabolism. Sinomenine is a compound extracted from the traditional Chinese herb sinomenium acutum (Thunb.) Rehd. et Wils. It has been used to treat NSCLC (non-small-cell lung cancer) and RA (rheumatoid arthritis) in some studies, but with limited understanding of its mechanisms.This study aims to examine the inhibitory effect of sinomenine hydrochloride (SH) on NSCLC and RA and to understand the underlying joint mechanisms.The results indicate that SH has a cytotoxic effect specifically on tumor cells, but not on normal cells. SH was found to induce cell apoptosis by activating the AMPK-mTOR pathway. Additionally, in autoimmune disease cell models, SH was shown to reduce the growth of RA-FLS cells by inhibiting the phosphorylation of AMPK, while having no effect on normal macrophages. Moreover, in vivo studies also showed that SH could reduce the production of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 and slow the development of adjuvant arthritis in rats. Furthermore, SH was found to significantly suppress tumor growth in a tumor xenograft experiment in mice.This study provides new insights into the treatment of tumors and autoimmune diseases by demonstrating that SH can selectively inhibit the growth of NSCLC cells and the progression of RA through activation of the AMPK pathway.Copyright © 2023 Elsevier GmbH. All rights reserved.