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[葛根通过抑制组蛋白去甲基化酶LSD1抗肺癌的机制]

[Mechanism of Puerariae Lobatae Radix against lung cancer by inhibiting histone demethylase LSD1].

作者信息

Qin Ting-Ting, Ma Jin-Lian, Yuan Yong, DU Kun, Miao Jin-Xin, Li Xiao-Fang, Zeng Hua-Hui, Wu Xiang-Xiang, Li Zhong-Hua

机构信息

Academy of Chinese Medical Sciences, Henan University of Chinese Medicine Zhengzhou 450046, China School of Pharmacy, Henan University of Chinese Medicine Zhengzhou 450046, China.

Academy of Chinese Medical Sciences, Henan University of Chinese Medicine Zhengzhou 450046, China.

出版信息

Zhongguo Zhong Yao Za Zhi. 2022 Oct;47(20):5574-5583. doi: 10.19540/j.cnki.cjcmm.20220421.705.

Abstract

Histone lysine-specific demethylase 1(LSD1) has become a promising molecular target for lung cancer therapy. Upon the screening platform for LSD1 activity, some Chinese herbal extracts were screened for LSD1 activity inhibition, and the underlying mechanism was preliminarily investigated at both molecular and cellular levels. The results of LSD1 inhibition showed that Puerariae Lobatae Radix extract can effectively reduce LSD1 expression to elevate the expression of H3 K4 me2 and H3 K9 me2 substrates in H1975 and H1299 cells. Furthermore, Puerariae Lobatae Radix was evaluated for its anti-lung cancer activity. It had a potent inhibitory ability against the proliferation and colony formation of both H1975 and H1299 cells. Flow cytometry and DAPI staining assays indicated that Puerariae Lobatae Radix can induce the apoptosis of lung cancer cells. In addition, it can significantly suppress the migration and reverse the epithelial-mesenchymal transition(EMT) process of lung cancer cells by activating E-cadherin and suppressing the expression of N-cadherin, slug and vimentin. To sum up, Puerariae Lobatae Radix displayed a robust inhibitory activity against lung cancer, and the mechanism may be related to the down-regulation of LSD1 expression to induce the cell apoptosis and suppress the cell migration and EMT process. These findings will provide new insights into the action of Puerariae Lobatae Radix as an anti-lung cancer agent and offer new ideas for the study on the anti-cancer action of Chinese medicine based on the epigenetic modification.

摘要

组蛋白赖氨酸特异性去甲基化酶1(LSD1)已成为肺癌治疗中一个有前景的分子靶点。在LSD1活性筛选平台上,筛选了一些中药提取物对LSD1活性的抑制作用,并在分子和细胞水平上初步研究了其潜在机制。LSD1抑制结果表明,葛根提取物可有效降低LSD1表达,从而提高H1975和H1299细胞中H3 K4 me2和H3 K9 me2底物的表达。此外,对葛根的抗肺癌活性进行了评估。它对H1975和H1299细胞的增殖和集落形成均具有强大的抑制能力。流式细胞术和DAPI染色分析表明,葛根可诱导肺癌细胞凋亡。此外,它可通过激活E-钙黏蛋白并抑制N-钙黏蛋白、蛞蝓蛋白和波形蛋白的表达,显著抑制肺癌细胞的迁移并逆转上皮-间质转化(EMT)过程。综上所述,葛根对肺癌表现出强大的抑制活性,其机制可能与下调LSD1表达以诱导细胞凋亡、抑制细胞迁移和EMT过程有关。这些发现将为葛根作为抗肺癌药物的作用提供新的见解,并为基于表观遗传修饰的中药抗癌作用研究提供新思路。

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