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泽漆提取物通过α丝氨酸/苏氨酸蛋白激酶和半胱天冬酶-3抑制乙型肝炎病毒相关肝细胞癌。

Euphorbia helioscopia L. extract suppresses hepatitis B virus-related hepatocellular carcinoma via alpha serine/threonine-protein kinase and Caspase-3.

作者信息

Xiong Dan, Gong Minyong, Hou Yanjun, Chen Haibing, Gao Tiexin, He Liuxin

机构信息

Department of Psychiatry 2, The Fifth People's Hospital of Jiujiang, Jiujiang, 332000, China.

Department of Oncology, Hospital of Traditional Chinese Medicine of Jiujiang, No. 555, Dehua Road, Wuli Street, Lianxi District, Jiujiang City, 332000, Jiangxi Province, China.

出版信息

J Cancer Res Clin Oncol. 2024 Oct 2;150(10):442. doi: 10.1007/s00432-024-05972-3.

DOI:10.1007/s00432-024-05972-3
PMID:39356361
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11446964/
Abstract

BACKGROUND

Hepatitis B virus (HBV)-related hepatocellular carcinoma (HBV-HCC) has poor prognosis and high mortality rate. Euphorbia helioscopia L. (EHL) is a classic Chinese medicinal herb.

AIM

This study aimed to evaluate in vitro anti-HBV-HCC properties of EHL, and explore it targets in HBV-HCC based on molecular docking.

METHODS

The anti-tumor effect of EHL on HBV-HCC was evaluated using the cell viability, migration, invasion, and apoptosis of Hep 3B2.1-7 and HepG2.2.15 cells. Next, network pharmacological analysis was performed to predicted the key targets of EHL against HBV-HCC. Then the prognostic targets, including RAC-alpha serine/threonine-protein kinase (AKT1) and Caspase-3 (CASP3), were verified using molecular docking and rescue experiments.

RESULTS

EHL exhibited inhibitory effects on cell proliferation/migration/invasion and induced cell apoptosis. Network pharmacological analysis proposed 12 active compounds in EHL, which targeted 22 HBV-HCC-related genes. AKT1 and CASP3 were identified to be key targets for EHL against HBV-HCC. AKT1 and CASP3 had prognostic significance in liver cancer. Overexpression of AKT1 and caspase-3 inhibitor can counteract the EHL effect.

CONCLUSION

EHL can exert anticancer effects on HBV-HCC by inhibiting migration/invasion, and inducing apoptosis, which may be achieved through AKT1 and CASP3.

摘要

背景

乙型肝炎病毒(HBV)相关肝细胞癌(HBV-HCC)预后较差,死亡率较高。泽漆是一种经典的中草药。

目的

本研究旨在评估泽漆对HBV-HCC的体外抗HBV-HCC特性,并基于分子对接探索其在HBV-HCC中的靶点。

方法

使用Hep 3B2.1-7和HepG2.2.15细胞的细胞活力、迁移、侵袭和凋亡来评估泽漆对HBV-HCC的抗肿瘤作用。接下来,进行网络药理学分析以预测泽漆抗HBV-HCC的关键靶点。然后使用分子对接和拯救实验验证包括RAC-α丝氨酸/苏氨酸蛋白激酶(AKT1)和半胱天冬酶-3(CASP3)在内的预后靶点。

结果

泽漆对细胞增殖/迁移/侵袭具有抑制作用并诱导细胞凋亡。网络药理学分析提出泽漆中有12种活性化合物,它们靶向22个与HBV-HCC相关的基因。AKT1和CASP3被确定为泽漆抗HBV-HCC的关键靶点。AKT1和CASP3在肝癌中具有预后意义。AKT1的过表达和半胱天冬酶-3抑制剂可抵消泽漆的作用。

结论

泽漆可通过抑制迁移/侵袭和诱导凋亡对HBV-HCC发挥抗癌作用,这可能是通过AKT1和CASP3实现的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5ed/11446964/3d3c12bc6622/432_2024_5972_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5ed/11446964/f9f43a1b9e58/432_2024_5972_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5ed/11446964/f61400062801/432_2024_5972_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5ed/11446964/f96b0ee5db78/432_2024_5972_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5ed/11446964/d9be8b2d803e/432_2024_5972_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5ed/11446964/6fd16ca2968b/432_2024_5972_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5ed/11446964/3d3c12bc6622/432_2024_5972_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5ed/11446964/f9f43a1b9e58/432_2024_5972_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5ed/11446964/f61400062801/432_2024_5972_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5ed/11446964/f96b0ee5db78/432_2024_5972_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5ed/11446964/d9be8b2d803e/432_2024_5972_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5ed/11446964/6fd16ca2968b/432_2024_5972_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5ed/11446964/3d3c12bc6622/432_2024_5972_Fig6_HTML.jpg

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