Abstract
Osteosarcoma (OS) is the most common type of primary bone tumor in children and adults. Dangshen (Codonopsis pilosula) is a traditional Chinese medicine commonly used in the treatment of OS worldwide. However, the molecular mechanisms of Dangshen in OS remain unclear. Hence, in this study, we aimed to systematically explore the underlying mechanisms of Dangshen in the treatment of OS. Our study adopted a network pharmacology approach, focusing on the identification of active ingredients, drug target prediction, gene collection, gene ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and other network tools. The network analysis identified 15 active compounds in Dangshen that were linked to 48 possible therapeutic targets related to OS. The results of the gene enrichment analysis show that Dangshen produces a therapeutic effect in OS likely by regulating multiple pathways associated with DNA damage, cell proliferation, apoptosis, invasion, and migration. Based on the network pharmacology approach, we successfully predicted the active compounds and their respective targets. In addition, we illustrated the molecular mechanisms that mediate the therapeutic effect of Dangshen in OS. These findings may aid in the development of novel targeted therapies for OS in the future.
Highlights
Osteosarcoma (OS) is the most common type of cancer of the bones
A flowchart of the study design is shown in Figure 1. e components of Dangshen were searched in the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database [21] and Traditional Chinese Medicines Integrated Database (TCMID) [22]
As suggested by the TCMSP database, Oral bioavailability (OB) ≥ 30% and DL ≥ 0.18 were used as the screening criteria, and the compounds whose OB ≥ 30% and DL ≥ 0.18 were selected for subsequent experiments [25]
Summary
Osteosarcoma (OS) is the most common type of cancer of the bones. It is a malignant tumor that primarily affects the long bones (e.g., legs), but it can start in other bones. Most OS patients present with metastatic disease, which contributes to its high morbidity and mortality rates worldwide. As of 2020, the standard treatment for OS is systemic chemotherapy [4], as the tumor is often resistant to radiation therapy. Surgical resection may be an option for patients diagnosed with locally noninvasive disease [5]. Most patients undergo multifaceted treatments that include preoperative chemotherapy, postoperative chemotherapy, surgical resection, and radiation therapy in rare cases [6]. Is makes it challenging to monitor disease progression and treatment response, which is why many physicians rely on long-term systemic chemotherapy [8]. The systemic chemotherapeutics needed to control the disease have serious adverse effects that further hinder the effective treatment of patients in the clinic [9]
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