基于生物信息学和体外实验探讨紫草素潜在的抗肿瘤机制

目的：紫草素（SHK），一种紫草根部的萘醌类活性成分，具有抗肿瘤活性。本研究通过生物信息学方法和细胞实验，探索SHK在肝细胞肝癌（LIHC）、前列腺腺癌（PRAD）和结肠腺癌（COAD）中的新靶点。方法：通过人类基因数据库（GeneCard）及癌症基因图谱（TCGA）获得SHK与3种癌症的交集基因，并进行基因本体（GO）和京都基因和基因组百科全书（KEGG）富集分析、蛋白质-蛋白质相互作用（PPT）网络构建等。体外实验检测SHK对人肝癌细胞（HepG2）、人前列腺癌细胞（LNCaP C4-2）和人结肠癌细胞（HT-29）的抑制作用，并分析SHK对细胞凋亡及预测靶点基因表达的影响。结果：SHK显著抑制3种癌细胞增殖并通过调节周期素依赖性激酶抑制因子1A（CDKN1A）等基因的表达实现抗肿瘤作用，且与生物信息学预测结果一致。此外，Kaplan-Meier生存曲线进一步表明CDKN1A等是SHK影响癌症患者生存的重要靶点；CDKN1A和B淋巴细胞瘤-2（BCL-2）是SHK抑制肿瘤细胞增殖和侵袭的核心靶点。结论：SHK可通过人体抑癌基因（P53）/CDKN1A和BCL-2/BCL-2关联X蛋白（BAX）通路诱导癌细胞凋亡。本研究报道了SHK抑制肿瘤的作用靶点及潜在机制，为含SHK的中草药作为抗肿瘤的潜在药物提供了初步依据。

Potential Mechanism of Shikonin in Treatment of Cancer Based on Bioinformatics and in Vitro Experiments

Shikonin(SHK),a naphthoquinone pigment-type active ingredient of lithospermum root,has anti-tumor activity.This study aims to identify novel targets of SHK in hepatocellular carcinoma(LIHC),prostate adenocarcinoma(PRAD),and colon adenocarcinoma(COAD) using bioinformatics methods and in vitro experiments.Methods:Intersection genes of SHK and three kinds of cancer were screened from GeneCard and TCGA databases.Gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analyses and protein-protein interaction(PPT) network construction were performed.The study detected the inhibitory effect of SHK on HepG2,LNCaP C4-2,and HT-29 cells through in vitro experiments and analyzed the effect of SHK on cell apoptosis and expression of predicted target genes.Results:SHK significantly inhibited the proliferation of three kinds of cancer cells and achieved the anti-tumor effect by regulating the expression of CDKN1A and other genes,which was consistent with the prediction of bioinformatics.In addition,the Kaplan-Meier survival curve further showed that CDKN1A and other genes were important targets of SHK affecting the survival of patients with cancer.CDKN1A and BCL-2 were the core targets of SHK in inhibiting the proliferation and invasion of cancer cells.Conclusion:SHK may induce cancer cell apoptosis through the P53/CDKN1A and BCL-2/BAX signaling pathways.The study reports the anti-tumor targets and underlying mechanisms of SHK,which provides preliminary evidence for the application of SHK-containing Chinese herbal medicine as a potential anti-tumor drug.