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中药方剂（益气健脾解毒方）治疗肝癌的体内外作用机制的研究

In Silico and In Vitro Studies on the Mechanisms of Chinese Medicine Formula (Yiqi Jianpi Jiedu Formula) in the Treatment of Hepatocellular Carcinoma.

机构信息

The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen 518033, China.

Shenzhen Traditional Chinese Medicine Hospital, Shenzhen 518033, China.

出版信息

Comput Math Methods Med. 2022 Oct 29;2022:8669993. doi: 10.1155/2022/8669993. eCollection 2022.

DOI:10.1155/2022/8669993
PMID:36345477
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9637043/
Abstract

OBJECTIVE

Traditional Chinese medicine (TCM) is an important part of the comprehensive treatment of hepatocellular carcinoma (HCC), and Chinese materia medica formulas with the effect of "Yiqi Jianpi" (replenishing qi and strengthening spleen) or "Jiedu" (removing toxicity) have been proved to be effective in treating HCC. However, mechanisms of these formulas in treating HCC remain unclear. In this paper, our goal is to explore the antitumor activity and its molecular mechanisms of Yiqi Jianpi Jiedu (YQJPJD) formula against HCC.

METHODS

The bioactive ingredients and targets of YQJPJD formula and HCC targets were screened by five Chinese materia medicas and two disease databases, respectively. The network pharmacology was utilized to construct the relationship network between YQJPJD formula and HCC, and the mechanisms were predicted by the protein-protein interaction (PPI) network, pathway enrichment analysis, bioinformatics, and molecular docking. Numerous in vitro assays were performed to verify the effect of YQJPJD formula on HCC cells, cancer-associated targets, and PI3K/Akt pathway.

RESULTS

The network relationship between YQJPJD formula and HCC suggested that YQJPJD formula mainly regulated the potential therapeutic targets of HCC by several key bioactive ingredients (e.g., quercetin, luteolin, baicalein, and wogonin). PPI network, bioinformatics, and molecular docking analyses displayed that YQJPJD formula may play an anti-HCC effect through key targets such as MAPK3, RAC1, and RHOA. Additionally, pathway analysis demonstrated that YQJPJD formula could play an anti-HCC effect via multiple pathways (e.g., PI3K-Akt and hepatitis B). Experimental results showed that YQJPJD formula could effectively inhibit the proliferation, migration, and invasion of HCC cells and promote HCC cell apoptosis in a concentration-dependent manner. Moreover, YQJPJD formula could decrease the mRNA expression of -catenin, MAPK3, and RHOA and the protein expression of phosphorylated PI3K and Akt.

CONCLUSION

YQJPJD formula mainly exerts its anti-HCC effect through multiple bioactive ingredients represented by quercetin, as well as multiple pathways and targets represented by PI3K/Akt pathway, -catenin, MAPK3, and RHOA.

摘要

目的

中药是肝癌综合治疗的重要组成部分，具有“益气健脾”或“解毒”作用的中药方剂已被证明对肝癌有效。然而，这些方剂治疗肝癌的机制尚不清楚。本文旨在探讨益气健脾解毒（YQJPJD）方对肝癌的抗肿瘤活性及其分子机制。

方法

分别采用五本中药和两个疾病数据库筛选 YQJPJD 方的生物活性成分和靶点以及 HCC 靶点。利用网络药理学构建 YQJPJD 方与 HCC 的关系网络，并通过蛋白质-蛋白质相互作用（PPI）网络、通路富集分析、生物信息学和分子对接预测机制。进行了大量的体外实验来验证 YQJPJD 方对 HCC 细胞、癌症相关靶点和 PI3K/Akt 通路的作用。

结果

YQJPJD 方与 HCC 的网络关系表明，YQJPJD 方主要通过几种关键生物活性成分（如槲皮素、木犀草素、黄芩素和白杨素）调节 HCC 的潜在治疗靶点。PPI 网络、生物信息学和分子对接分析显示，YQJPJD 方可能通过关键靶点如 MAPK3、RAC1 和 RHOA 发挥抗 HCC 作用。此外，通路分析表明，YQJPJD 方可以通过多种途径（如 PI3K-Akt 和乙型肝炎）发挥抗 HCC 作用。实验结果表明，YQJPJD 方可以有效抑制 HCC 细胞的增殖、迁移和侵袭，并促进 HCC 细胞凋亡，呈浓度依赖性。此外，YQJPJD 方可以降低-catenin、MAPK3 和 RHOA 的 mRNA 表达以及磷酸化 PI3K 和 Akt 的蛋白表达。

结论

YQJPJD 方主要通过以槲皮素为代表的多种生物活性成分以及以 PI3K/Akt 通路、-catenin、MAPK3 和 RHOA 为代表的多种途径和靶点发挥抗 HCC 作用。

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