目的 運用網(wǎng)絡(luò)藥理學(xué)和分子對接方法探究黃精抗肝細(xì)胞癌的潛在作用機制。方法 通過BATMAN-TCM 2.0、GeneCards、OMIM等數(shù)據(jù)庫獲取黃精活性成分靶點及肝細(xì)胞癌相關(guān)靶點，篩選交集靶點后構(gòu)建蛋白質(zhì)相互作用（PPI）網(wǎng)絡(luò)，識別核心靶點。利用DAVID數(shù)據(jù)庫進(jìn)行基因本體（GO）和京都基因與基因組百科全書（KEGG）通路富集分析，挖掘關(guān)鍵生物過程和信號通路。結(jié)合GEO、GEPIA2等數(shù)據(jù)庫進(jìn)行單基因差異表達(dá)和生存分析，篩選關(guān)鍵基因。通過PDB數(shù)據(jù)庫獲取關(guān)鍵靶點蛋白三維結(jié)構(gòu)，利用AutoDockTools軟件進(jìn)行黃精活性成分與靶點的分子對接，分析結(jié)合能。結(jié)果 共獲得478個黃精與肝細(xì)胞癌交集靶點，核心靶點涉及腫瘤蛋白p53（TP53）、蛋白激酶B1（Akt1）、表皮生長因子受體（EGFR）等關(guān)鍵調(diào)控因子。GO富集顯示靶點主要參與跨膜離子轉(zhuǎn)運、細(xì)胞應(yīng)激反應(yīng)等生物過程；KEGG通路富集到193條通路，其中抑制磷脂酰肌醇3激酶（PI3K）/蛋白激酶B（Akt）/哺乳動物雷帕霉素靶蛋白（mTOR）、絲裂原激活的蛋白激酶（MAPK）、Wnt通路為關(guān)鍵通路。單基因分析顯示人雌激素受體1（ESR1）、絲裂原活化蛋白激酶3（MAPK3）、基質(zhì)金屬蛋白酶9（MMP9）在肝細(xì)胞癌中表達(dá)異常且與預(yù)后相關(guān)。黃精主要活性成分可能為黃芩素、甘草苷、去甲烏藥堿等。分子對接證實其與核心靶點結(jié)合能均小于−5.0 kcal/mol，部分小于−7.0 kcal/mol，結(jié)合活性較強。結(jié)論 黃精通過多靶點（如TP53、Akt1、EGFR）調(diào)控PI3K/Akt/mTOR、MAPK、Wnt等信號通路抑制肝細(xì)胞癌增殖、誘導(dǎo)凋亡并干預(yù)轉(zhuǎn)移過程。

Objective To explore the potential mechanism of Polygonatum sibiricum against hepatocellular carcinoma based on network pharmacology and molecular docking. Methods The active ingredient targets of P. sibiricum and hepatocellular carcinoma related targets were obtained from databases such as BATMAN-TCM 2.0, GeneCards, OMIM, etc. After screening for intersecting targets, a protein-protein interaction (PPI) network was constructed to identify core targets. Perform gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis using the DAVID database to identify key biological processes and signaling pathways. Combined with GEO, GEPIA2 and other databases, single gene differential expression and survival analysis were performed to screen key genes. Obtain the three-dimensional structure of key target proteins from the RCSB PDB database, and use AutoDockTools software to perform molecular docking between the active ingredients of P. sibiricum and the targets, analyzing the binding energy. Results A total of 478 intersecting targets between P. sibiricum and hepatocellular carcinoma were obtained, with core targets involving tumor protein p53 (TP53), protein kinase B1 (Akt1), and epidermal growth factor receptor (EGFR). GO enrichment showed that the target was mainly involved in biological processes such as transmembrane ion transport and cell stress response. The KEGG pathway was enriched to 193 pathways, among which the inhibition of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), mitogen-activated protein kinase (MAPK), and Wnt pathway were the key pathways. Single gene analysis showed that human estrogen receptor 1 (ESR1), mitogen-activated protein kinase 3 (MAPK3), and matrix metalloproteinase 9 (MMP9) were abnormally expressed in hepatocellular carcinoma and were associated with prognosis. The main active components of P. sibiricum may be baicalein, liquiritin, higenamine, etc. Molecular docking confirmed that the binding energy with the core target was less than − 5.0 kcal/mol, some less than −7.0 kcal/mol, and the binding activity was strong. Conclusion P. sibiricum inhibits proliferation, induces apoptosis and interferes with metastasis of hepatocellular carcinoma by regulating PI3K/Akt/mTOR, MAPK, Wnt and other signaling pathways through multiple targets (such as TP53, Akt1, EGFR).

R285

湖北省中醫(yī)藥管理局中醫(yī)藥科研項目（ZY2023M036）