"黄连解毒片 "通过下调 PI3K/AKT/mTOR 和 MAPK/ERK1/2 信号通路抗胰腺癌增殖

IF 3.3 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE
Shu Dong Md, Panling Xu Md, Peiwen Yang Md, Juying Jiao Md, Chien-Shan Cheng Md PhD, Lianyu Chen Md PhD
{"title":"\"黄连解毒片 \"通过下调 PI3K/AKT/mTOR 和 MAPK/ERK1/2 信号通路抗胰腺癌增殖","authors":"Shu Dong Md, Panling Xu Md, Peiwen Yang Md, Juying Jiao Md, Chien-Shan Cheng Md PhD, Lianyu Chen Md PhD","doi":"10.1177/2515690X241291381","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Huanglianjiedu decoction (HLJDD) is a classical Traditional Chinese Medicine (TCM) prescription with thousand years of clinical use against various malignancies, including pancreatic adenocarcinoma (PAAD). However, its potential bioactive component and molecular mechanism remains unclear.</p><p><strong>Aims: </strong>This study is to inspect the HLJDD mechanisms of action against PAAD via integrated computational and pharmacochemistry strategy, <i>in vivo</i> and <i>in vitro</i> experiments to validate associated targets and pathways.</p><p><strong>Methods: </strong>A PAAD xenograft model was established by subcutaneous injecting Panc02 cells into C57BL/6 mice. Ultra-high performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) was engaged to determine constituents of HLJDD and assessed for pharmacokinetic scheme using the TCM Systems Pharmacology Platform (TCM-SP). Differentially expressed genes (DEGs) of PAAD was retrieved from the transcriptome dataset GSE43795, followed by recognizing overlapping targets the oncogenes and target genes of PAAD and HLJDD, respectively. Putative signaling pathways of HLJDD in treating PAAD were enriched using KEGG and GO analyses. The anti-PAAD effects of HLJDD was assessed <i>in vivo</i> and <i>in vitro</i>, besides, the potential mechanism was validated using immunoblotting and immunohistochemical assays.</p><p><strong>Results: </strong>HLJDD significantly suppressed the growth of transplanted PAAD tumors, constrained PAAD progression, and induced apoptosis and S-phase arrest. Seventy-five active components meeting the drug-likeness criteria and 278 target genes of HLJDD were identified. KEGG analysis indicated that the top three enriched pathways were cancer, AGE-RAGE signaling, and IL-17 signaling pathways. Disease enrichment analysis highlighted immune, pharmacological, and cancer-related diseases as the top three categories. A total of 47 potential target genes were identified. Immunoblotting revealed that HLJDD inhibited PI3K and MAPK-related signaling pathways, while immunohistochemical staining confirmed that HLJDD suppressed the expression of phosphorylated MAPK and ERK1/2.</p><p><strong>Conclusion: </strong>HLJDD inhibited PAAD <i>in vitro</i> and <i>in vivo</i> via the modulation of multiple mechanisms, including regulation of PI3K/AKT/mTOR and MAPK/ERK1/2 signaling pathways.</p>","PeriodicalId":15714,"journal":{"name":"Journal of Evidence-based Integrative Medicine","volume":"29 ","pages":"2515690X241291381"},"PeriodicalIF":3.3000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11489918/pdf/","citationCount":"0","resultStr":"{\"title\":\"\\\"Huanglianjiedu Decoction\\\" Against Pancreatic Adenocarcinoma Proliferation of by Downregulating the PI3K/AKT/mTOR and MAPK/ERK1/2 Signaling Pathways.\",\"authors\":\"Shu Dong Md, Panling Xu Md, Peiwen Yang Md, Juying Jiao Md, Chien-Shan Cheng Md PhD, Lianyu Chen Md PhD\",\"doi\":\"10.1177/2515690X241291381\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Huanglianjiedu decoction (HLJDD) is a classical Traditional Chinese Medicine (TCM) prescription with thousand years of clinical use against various malignancies, including pancreatic adenocarcinoma (PAAD). However, its potential bioactive component and molecular mechanism remains unclear.</p><p><strong>Aims: </strong>This study is to inspect the HLJDD mechanisms of action against PAAD via integrated computational and pharmacochemistry strategy, <i>in vivo</i> and <i>in vitro</i> experiments to validate associated targets and pathways.</p><p><strong>Methods: </strong>A PAAD xenograft model was established by subcutaneous injecting Panc02 cells into C57BL/6 mice. Ultra-high performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) was engaged to determine constituents of HLJDD and assessed for pharmacokinetic scheme using the TCM Systems Pharmacology Platform (TCM-SP). Differentially expressed genes (DEGs) of PAAD was retrieved from the transcriptome dataset GSE43795, followed by recognizing overlapping targets the oncogenes and target genes of PAAD and HLJDD, respectively. Putative signaling pathways of HLJDD in treating PAAD were enriched using KEGG and GO analyses. The anti-PAAD effects of HLJDD was assessed <i>in vivo</i> and <i>in vitro</i>, besides, the potential mechanism was validated using immunoblotting and immunohistochemical assays.</p><p><strong>Results: </strong>HLJDD significantly suppressed the growth of transplanted PAAD tumors, constrained PAAD progression, and induced apoptosis and S-phase arrest. Seventy-five active components meeting the drug-likeness criteria and 278 target genes of HLJDD were identified. KEGG analysis indicated that the top three enriched pathways were cancer, AGE-RAGE signaling, and IL-17 signaling pathways. Disease enrichment analysis highlighted immune, pharmacological, and cancer-related diseases as the top three categories. A total of 47 potential target genes were identified. Immunoblotting revealed that HLJDD inhibited PI3K and MAPK-related signaling pathways, while immunohistochemical staining confirmed that HLJDD suppressed the expression of phosphorylated MAPK and ERK1/2.</p><p><strong>Conclusion: </strong>HLJDD inhibited PAAD <i>in vitro</i> and <i>in vivo</i> via the modulation of multiple mechanisms, including regulation of PI3K/AKT/mTOR and MAPK/ERK1/2 signaling pathways.</p>\",\"PeriodicalId\":15714,\"journal\":{\"name\":\"Journal of Evidence-based Integrative Medicine\",\"volume\":\"29 \",\"pages\":\"2515690X241291381\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2024-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11489918/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Evidence-based Integrative Medicine\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1177/2515690X241291381\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"INTEGRATIVE & COMPLEMENTARY MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Evidence-based Integrative Medicine","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1177/2515690X241291381","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"INTEGRATIVE & COMPLEMENTARY MEDICINE","Score":null,"Total":0}
引用次数: 0

摘要

背景:黄连解毒汤(HLJDD)是一种经典的中药处方,在临床上用于治疗包括胰腺癌(PAAD)在内的多种恶性肿瘤已有上千年的历史。目的:本研究旨在通过综合计算和药理化学策略、体内和体外实验验证相关靶点和通路,从而研究 HLJDD 对 PAAD 的作用机制:方法:通过向C57BL/6小鼠皮下注射Panc02细胞建立PAAD异种移植模型。采用超高效液相色谱-串联质谱法(UHPLC-MS/MS)测定HLJDD的成分,并利用中医药系统药理学平台(TCM-SP)评估药代动力学方案。从转录组数据集 GSE43795 中检索 PAAD 的差异表达基因(DEGs),然后分别识别 PAAD 和 HLJDD 的癌基因和靶基因的重叠靶点。通过 KEGG 和 GO 分析富集了 HLJDD 治疗 PAAD 的可能信号通路。在体内和体外评估了HLJDD抗PAAD的作用,并通过免疫印迹和免疫组化实验验证了其潜在机制:结果:HLJDD能明显抑制移植PAAD肿瘤的生长,抑制PAAD的进展,诱导细胞凋亡和S期停滞。结果:HLJDD能明显抑制移植PAAD肿瘤的生长,抑制PAAD的进展,诱导细胞凋亡和S期停滞。KEGG分析表明,癌症、AGE-RAGE信号转导和IL-17信号转导通路是前三个富集通路。疾病富集分析显示,免疫疾病、药理疾病和癌症相关疾病是前三类疾病。共鉴定出 47 个潜在靶基因。免疫印迹显示,HLJDD抑制了PI3K和MAPK相关信号通路,而免疫组化染色证实,HLJDD抑制了磷酸化MAPK和ERK1/2的表达:结论:HLJDD通过调节PI3K/AKT/mTOR和MAPK/ERK1/2信号通路等多种机制抑制体外和体内的PAAD。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
"Huanglianjiedu Decoction" Against Pancreatic Adenocarcinoma Proliferation of by Downregulating the PI3K/AKT/mTOR and MAPK/ERK1/2 Signaling Pathways.

Background: Huanglianjiedu decoction (HLJDD) is a classical Traditional Chinese Medicine (TCM) prescription with thousand years of clinical use against various malignancies, including pancreatic adenocarcinoma (PAAD). However, its potential bioactive component and molecular mechanism remains unclear.

Aims: This study is to inspect the HLJDD mechanisms of action against PAAD via integrated computational and pharmacochemistry strategy, in vivo and in vitro experiments to validate associated targets and pathways.

Methods: A PAAD xenograft model was established by subcutaneous injecting Panc02 cells into C57BL/6 mice. Ultra-high performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) was engaged to determine constituents of HLJDD and assessed for pharmacokinetic scheme using the TCM Systems Pharmacology Platform (TCM-SP). Differentially expressed genes (DEGs) of PAAD was retrieved from the transcriptome dataset GSE43795, followed by recognizing overlapping targets the oncogenes and target genes of PAAD and HLJDD, respectively. Putative signaling pathways of HLJDD in treating PAAD were enriched using KEGG and GO analyses. The anti-PAAD effects of HLJDD was assessed in vivo and in vitro, besides, the potential mechanism was validated using immunoblotting and immunohistochemical assays.

Results: HLJDD significantly suppressed the growth of transplanted PAAD tumors, constrained PAAD progression, and induced apoptosis and S-phase arrest. Seventy-five active components meeting the drug-likeness criteria and 278 target genes of HLJDD were identified. KEGG analysis indicated that the top three enriched pathways were cancer, AGE-RAGE signaling, and IL-17 signaling pathways. Disease enrichment analysis highlighted immune, pharmacological, and cancer-related diseases as the top three categories. A total of 47 potential target genes were identified. Immunoblotting revealed that HLJDD inhibited PI3K and MAPK-related signaling pathways, while immunohistochemical staining confirmed that HLJDD suppressed the expression of phosphorylated MAPK and ERK1/2.

Conclusion: HLJDD inhibited PAAD in vitro and in vivo via the modulation of multiple mechanisms, including regulation of PI3K/AKT/mTOR and MAPK/ERK1/2 signaling pathways.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Journal of Evidence-based Integrative Medicine
Journal of Evidence-based Integrative Medicine INTEGRATIVE & COMPLEMENTARY MEDICINE-
CiteScore
5.90
自引率
0.00%
发文量
43
审稿时长
15 weeks
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信