Research Paper Volume 15, Issue 11 pp 5125—5143
Network pharmacology-based research on the effect of angelicin on osteosarcoma and the underlying mechanism
- 1 Department of Traumatology and Orthopaedics, Affiliated Hospital of Chengde Medical University, Chengde 067000, Hebei, China
- 2 Department of General Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
- 3 Central Laboratory, Affiliated Hospital of Chengde Medical University, Chengde 067000, Hebei, China
Received: December 28, 2022 Accepted: May 9, 2023 Published: June 10, 2023
https://doi.org/10.18632/aging.204786How to Cite
Copyright: © 2023 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
To explore the antitumor effects of angelicin on osteosarcoma and the underlying mechanism. We aimed to elucidate the mechanism by network pharmacology, molecular docking, and in vitro experiments. We analyzed a PPI network of potential angelicin targets in the treatment of osteosarcoma and identified hub targets. We systematically performed GO and KEGG enrichment analyses of the potential targets of angelicin, and we predicted it function in osteosarcoma treatment and the underlying molecular mechanism. Through molecular docking, the interactions between hub targets and angelicin were simulated, and then, the hub targets of angelicin were identified. Based on these results, we validated the effects of angelicin on osteosarcoma cells by conducting in vitro experiments. The PPI network analysis of potential therapeutic targets identified four apoptosis-related hub targets, namely, BCL-2, Casp9, BAX and BIRC 2. GO and KEGG enrichment analyses demonstrated that angelicin regulates osteosarcoma cell apoptosis. Molecular docking results indicated that angelicin can freely bind to the hub targets listed above. In vitro experiments showed that angelicin promoted osteosarcoma cell apoptosis in a dose-dependent manner and inhibited osteosarcoma cell migration and proliferation in a time- and dose-dependent manner. The RT-PCR results showed that angelicin simultaneously promoted the mRNA expression of Bcl-2 and Casp9 and inhibited the mRNA expression of BAX and BIRC 2. Angelicin promotes osteosarcoma cell apoptosis and inhibits osteosarcoma cell proliferation and migration by activating a signaling network that is composed of hub targets that link multiple signaling pathways. Angelicin could become an alternative drug for the treatment of osteosarcoma.
Abbreviations
RT-PCR: reverse transcription-polymerase chain reaction; BAX: BCL2-associated X protein; BCL-2: B-cell lymphoma-2; BIRC 2: baculoviral IAP repeat-containing protein 2; Casp9: caspase 9; OS: osteosarcoma; NIH: National Institutes of Health; BP: biological process; CC: cellular component; MF: molecular function; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; PPI: protein-protein interaction; CCK8: Cell Counting Kit-8; DMSO: dimethyl sulfoxide; MEM: minimum essential medium; PI: propidium iodide; FITC: fluorescein isothiocyanate; P53: tumor antigen p53; NF-κB: NF-kappa-B; TNF: tumor necrosis factor; MEM: modified Eagle’s medium; FBS: fetal bovine serum(FBS).