PurposeThe objective of this research was to employ network pharmacology to analyze and identify the key active components and target points of action of Aidi injection in relation to colorectal cancer. Additionally, this study aimed to experimentally validate the mechanism of action of hinokinin in treating colorectal cancer.MethodsThis study employed a network pharmacology methodology to identify the primary components and action targets of Aidi injection in public databases; a similar approach was used to identify effective targets for colorectal cancer treatment. The protein‒protein interaction network, along with gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses, facilitated the prediction of central targets and pathways by which Aidi injection combats colorectal cancer. Molecular docking techniques were harnessed to sift through drugs and their targets for high binding affinity. Experimental validation was carried out to corroborate the findings derived from network pharmacology.ResultsWe identified 37 active constituents of Aidi injection (ADI), 701 potential targets, 768 colorectal cancer (CRC) targets, and 111 overlapping targets. The anti-CRC efficacy of ADI seems to be associated with several pathways: cancer pathways, EGFR tyrosine kinase inhibitor resistance, proteoglycans in cancer, endocrine resistance, central carbon metabolism in cancer, chemo-oncogenic receptor initiation, cancer-specific microRNAs, and signaling pathways such as PI3K-Akt, mitogen-activated protein kinase, prolactin, FoxO, and Ras. Predominantly, ADI exhibited activity against key markers such as EGFR, ERBB2, HSP90AA1, mTOR, HIF1A, CCND1, JUN, AKT1, SRC, and STAT3 to mitigate CRC. Furthermore, Hinokinin has been shown to curtail the proliferation of colorectal cancer cells, amplify apoptosis, and modulate the expression of the mTOR protein.ConclusionThrough network pharmacology, we identified 13 shared targets associated with colorectal cancer. Subsequent experimental validation revealed that hinokinin can curtail the proliferation of colorectal cancer cells and enhance their apoptosis, primarily by modulating mTOR expression.

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艾迪注射液治疗结直肠癌的网络药理学方法及部分实验验证

目的本研究旨在运用网络药理学分析鉴定艾迪注射液治疗结直肠癌的关键活性成分及作用靶点。此外，本研究旨在通过实验验证桧木素治疗结直肠癌的作用机制。方法本研究采用网络药理学方法，在公共数据库中鉴定艾迪注射液的主要成分和作用靶点；使用类似的方法来确定结直肠癌治疗的有效靶标。蛋白质-蛋白质相互作用网络，以及基因本体论和京都基因与基因组百科全书通路富集分析，促进了艾迪注射液抗结直肠癌的中心靶点和通路的预测。利用分子对接技术筛选药物及其靶标以获得高结合亲和力。我们进行了实验验证，以证实网络药理学的结果。结果我们鉴定了艾迪注射液（ADI）的37个活性成分、701个潜在靶点、768个结直肠癌（CRC）靶点和111个重叠靶点。 ADI 的抗 CRC 功效似乎与多种途径相关：癌症途径、EGFR 酪氨酸激酶抑制剂耐药性、癌症中的蛋白聚糖、内分泌耐药性、癌症中的中心碳代谢、化疗致癌受体启动、癌症特异性 microRNA 和信号传导PI3K-Akt、丝裂原激活蛋白激酶、催乳素、FoxO 和 Ras 等途径。 ADI 主要表现出针对 EGFR、ERBB2、HSP90AA1、mTOR、HIF1A、CCND1、JUN、AKT1、SRC 和 STAT3 等关键标志物的活性，可减轻 CRC。此外，Hinokinin 已被证明可以抑制结直肠癌细胞的增殖、放大细胞凋亡并调节 mTOR 蛋白的表达。结论通过网络药理学，我们确定了 13 个与结直肠癌相关的共同靶点。随后的实验验证表明，日桧素主要通过调节 mTOR 表达来抑制结直肠癌细胞的增殖并增强其凋亡。