Uncovering the mechanism of Kang-ai injection for treating intrahepatic cholangiocarcinoma based on network pharmacology, molecular docking, and in vitro validation

Fei Song; Chang-Liang Lu; Cheng-Gui Wang; Chen-Wei Hu; Yu Zhang; Tian-Lun Wang; Lu Han; Zhong Chen

doi:10.3389/fphar.2023.1129709

Uncovering the mechanism of Kang-ai injection for treating intrahepatic cholangiocarcinoma based on network pharmacology, molecular docking, and in vitro validation

Front Pharmacol. 2023 Mar 2:14:1129709. doi: 10.3389/fphar.2023.1129709. eCollection 2023.

Authors

Fei Song¹, Chang-Liang Lu¹, Cheng-Gui Wang¹, Chen-Wei Hu¹, Yu Zhang¹, Tian-Lun Wang¹, Lu Han², Zhong Chen¹

Affiliations

¹ Department of Hepatobiliary Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China.
² Jiangsu Vocational College of Medicine, Yancheng, China.

Abstract

Objective: 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 in vitro validation. Methods: 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. In vitro experiments were carried out to validate the findings. Results: 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 in vitro 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. Conclusion: 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.

Keywords: Kang-ai injection; PI3K/Akt signaling pathway; intrahepatic cholangiocarcinoma; molecular docking; network pharmacology.

Grants and funding

This study was supported by the National Natural Science Foundation of China grants (81871927 and 81070360), 2021 Changchun University of Chinese Medicine School-level Clinical Practice Teaching Reform Special Research Project (XJLCSJ202146), and the Nantong Hepatobiliary and Pancreatic Surgery Disease Research Center Construction Project (HS2015001).