Song Fei, Lu Chang-Liang, Wang Cheng-Gui, Hu Chen-Wei, Zhang Yu, Wang Tian-Lun, Han Lu, Chen Zhong
Department of Hepatobiliary Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China.
Jiangsu Vocational College of Medicine, Yancheng, China.
Front Pharmacol. 2023 Mar 2;14:1129709. doi: 10.3389/fphar.2023.1129709. eCollection 2023.
Kang-ai injection (KAI) has been a popular adjuvant treatment for solid tumors, but its anti-tumor mechanism in intrahepatic cholangiocarcinoma (ICC) remains poorly understood. This study applied a network pharmacology-based approach to unveil KAI's anti-tumor activity, key targets, and potential pharmacological mechanism in ICC by integrating molecular docking and validation. The KAI-compound-target-ICC network was constructed to depict the connections between active KAI compounds and ICC-related targets based on the available data sources. The crucial ingredients, potential targets, and signaling pathways were screened using GO, KEGG enrichment analysis, and the PPI network. Molecular docking was performed to visualize the interactions between hub targets and components. experiments were carried out to validate the findings. Among the 87 active components of KAI and 80 KAI-ICC-related targets, bioinformatics analysis identified quercetin as a possible candidate. GO and KEGG enrichment analysis indicated that the PI3K-AKT signaling pathway might be essential in ICC pharmacotherapy. The PPI network and its sub-networks screened 10 core target genes, including AKT1 and IL1β. Molecular docking results showed stable binding between AKT1 and IL1β with KAI active ingredients. The experiments confirmed that KAI might suppress the proliferation of ICC cell lines by inhibiting the PI3K/AKT signaling pathway, consistent with the network pharmacology approach and molecular docking predictions. The study sheds light on KAI's biological activity, potential targets, and molecular mechanisms in treating ICC and provides a promising strategy for understanding the scientific basis and therapeutic mechanisms of herbal treatments for ICC. This research has important implications for developing new, targeted therapies for ICC and highlights the importance of network pharmacology-based approaches in investigating complex herbal formulations.
康艾注射液（KAI）一直是实体瘤常用的辅助治疗药物，但其在肝内胆管癌（ICC）中的抗肿瘤机制仍不清楚。本研究采用基于网络药理学的方法，通过整合分子对接和验证，揭示KAI在ICC中的抗肿瘤活性、关键靶点及潜在药理机制。基于现有数据源构建KAI-化合物-靶点-ICC网络，以描述活性KAI化合物与ICC相关靶点之间的联系。利用基因本体论（GO）、京都基因与基因组百科全书（KEGG）富集分析和蛋白质-蛋白质相互作用（PPI）网络筛选关键成分、潜在靶点和信号通路。进行分子对接以可视化枢纽靶点与成分之间的相互作用。开展实验验证研究结果。在KAI的87种活性成分和80个与KAI-ICC相关的靶点中，生物信息学分析确定槲皮素为可能的候选物。GO和KEGG富集分析表明，PI3K-AKT信号通路可能在ICC药物治疗中起关键作用。PPI网络及其子网筛选出10个核心靶基因，包括AKT1和IL1β。分子对接结果显示AKT1和IL1β与KAI活性成分之间具有稳定结合。实验证实，KAI可能通过抑制PI3K/AKT信号通路抑制ICC细胞系的增殖，这与网络药理学方法和分子对接预测结果一致。该研究揭示了KAI在治疗ICC中的生物学活性、潜在靶点和分子机制，为理解ICC草药治疗的科学依据和治疗机制提供了一种有前景的策略。本研究对开发针对ICC的新型靶向治疗具有重要意义，并凸显了基于网络药理学方法在研究复杂草药配方中的重要性。
