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问夏肠复方乙酸乙酯提取物通过调控 PI3K-AKT 信号通路抑制肺腺癌细胞的癌变。

The ethyl acetate extract of Wenxia Changfu Formula inhibits the carcinogenesis of lung adenocarcinoma by regulating PI3K-AKT signaling pathway.

机构信息

Department of Medicine, Jining No. 1 People's Hospital, No. 6 Jiankang Road, Rencheng District, Jining City, 272113, Shandong Province, China.

Emergency Medicine, Jining No. 1 People's Hospital, Jining City, Shandong Province, China.

出版信息

Sci Rep. 2023 Mar 22;13(1):4715. doi: 10.1038/s41598-023-31924-x.

DOI:10.1038/s41598-023-31924-x
PMID:36949111
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10033682/
Abstract

Lung adenocarcinoma is the most common type of lung cancer. With a rise in new cases worldwide each year, early diagnosis and treatment are very important. Network pharmacology provides the effective way to evaluate poly-pharmacological effects and anticancer molecular mechanisms of drugs. The aim of the present study was to explore the anti-tumor mechanism of ethyl acetate extract of Wenxia Changfu Formula (WFEA) in lung adenocarcinoma by using analytical chemistry, network pharmacology and molecular biology. A total of 193 compounds were identified from WFEA, mainly including esters, phenols, ketones and alkaloids. Totally, 374 targets were regarded as potential targets of WFEA against lung adenocarcinoma. Interestingly, PI3K-AKT was found to be one of the significantly enriched signaling pathways of targets of WFEA against lung adenocarcinoma. AKT1, MMP3, CASP3 and BCL2 had strong binding effect with compound molecules of WFEA. Some combinations with the best docking binding were identified, including quercetin/oleanolic_acid/emodin/aloe_emodin/catechin-AKT1 and quercetin-MMP3. In lung adenocarcinoma cells, the WFEA inhibited the proliferation, migration and invasion, and promoted the apoptosis. Moreover, the WFEA inhibited the mRNA expression of MMP3 and Bcl-2 and promoted the mRNA expression of Caspase3. In addition, WFEA inhibited the protein phosphorylation of AKT and PI3K. The WFEA had a significant inhibitory effect on lung adenocarcinoma cells, which could inhibit cell proliferation, invasion and metastasis, and induce cell apoptosis. The mechanism of action of WFEA may be involved in the regulation of the PI3K-AKT signaling pathway in the lung adenocarcinoma.

摘要

肺腺癌是最常见的肺癌类型。随着全球每年新发病例的增加，早期诊断和治疗非常重要。网络药理学为评估药物的多药理作用和抗癌分子机制提供了有效的方法。本研究旨在通过分析化学、网络药理学和分子生物学方法探讨温下肠复方（WFEA）乙酸乙酯提取物对肺腺癌的抗肿瘤作用机制。从 WFEA 中鉴定出 193 种化合物，主要包括酯类、酚类、酮类和生物碱类。总共将 374 个靶点视为 WFEA 治疗肺腺癌的潜在靶点。有趣的是，PI3K-AKT 被发现是 WFEA 治疗肺腺癌的靶点显著富集的信号通路之一。AKT1、MMP3、CASP3 和 BCL2 与 WFEA 化合物具有很强的结合作用。鉴定出一些具有最佳对接结合的组合，包括槲皮素/齐墩果酸/大黄素/芦荟大黄素/儿茶素-AKT1 和槲皮素-MMP3。在肺腺癌细胞中，WFEA 抑制增殖、迁移和侵袭，促进凋亡。此外，WFEA 抑制 MMP3 和 Bcl-2 的 mRNA 表达，促进 Caspase3 的 mRNA 表达。此外，WFEA 抑制 AKT 和 PI3K 的蛋白磷酸化。WFEA 对肺腺癌细胞具有显著的抑制作用，可抑制细胞增殖、侵袭和转移，并诱导细胞凋亡。WFEA 的作用机制可能涉及调节肺腺癌中的 PI3K-AKT 信号通路。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cf9/10033682/dc415d574bfd/41598_2023_31924_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cf9/10033682/bc13b14031a7/41598_2023_31924_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cf9/10033682/c0b4643d26f0/41598_2023_31924_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cf9/10033682/daf0ba4f42c5/41598_2023_31924_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cf9/10033682/d8a35eacfed4/41598_2023_31924_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cf9/10033682/3f99c6e50de8/41598_2023_31924_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cf9/10033682/355ec0f9a17b/41598_2023_31924_Fig11_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cf9/10033682/5f1e36855074/41598_2023_31924_Fig12_HTML.jpg

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