Title:A Network Pharmacology Guided Mechanism of Action Study on Oldenlandia
diffusa Against Osteosarcoma
Volume: 20
Issue: 8
Author(s): Jun Zhao, Liang Dong, Jun Wang, Boyu Pan and Yun Yang*
Affiliation:
- Department of Bone & Soft Tissue Tumor, Tianjin Medical University Cancer Institute & Hospital; National Clinical
Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy; Tianjin's Clinical Research Center for
Cancer, Tianjin 300060, China
Keywords:
Oldenlandia diffusa (OD), osteosarcoma (OS), network pharmacology, molecular docking, tradition chinese medicine (TCM), chinese herb medicine (CHM).
Abstract:
Background: Osteosarcoma (OS) is the most prevalent primary bone sarcoma in the global
child and young adult population, and the current mainstream treatment regimens are not very effective.
The unique efficacy of traditional Chinese medicine (TCM) for cancers has recently received increasing
attention. Oldenlandia diffusa (OD) is commonly used as adjuvant therapy for various cancers in Chinese
herb medicine (CHM) with its unique pharmacological activities, but its therapeutic effect as well as the
underlying mechanism against OS has yet to be systematically investigated.
Objective: This study aims to find the underlying active mechanism of OD against OS.
Methods: The candidate ingredients as well as drug targets of OD were obtained from the Traditional
Chinese Medicine System Pharmacology (TCMSP) database, respectively. Meanwhile, the OS diseaserelated
targets were acquired from GeneCards and MalaCards online databases. Then, by using Venny
2.1, the common key targets were imported into the STRING database to acquire their interaction relationship,
and imported this PPI network file (.csv) into Cytoscape 3.6.0 software and merged to obtain
PPI network intersections. Meanwhile, the MCODE plugin of Cytoscape was also used to further trim the
core therapeutic targets. GO and KEGG enrichment and molecular docking analyses were performed to
predict the underlying mechanism of OD against OS. Furthermore, in silico analysis results were validated
by a series of cellular functional and molecular biological assays.
Results: A total of 131 putative targets were identified to be involved in the anti-OS activity of OD. The
PPI network, GO as well as KEGG analyses revealed that the 18 core targets were closely related to cell
proliferation, apoptosis. Importantly, the subsequent in vitro assays verified that the suppressive effect of
OD on OS cell growth indeed resulted from disrupted apoptosis and cell proliferation via Akt and ERK
signaling pathways. Furthermore, our results showed that quercetin, beta-sitosterol and 2-methoxy-3-
methyl-9,10-anthraquinone were the key ingredients, while PTGS2, CASP3 and JUN were the key targets
in delivering the pharmacological activities of OD against OS, thus providing an insight into the anti-OS
action of OD from a holistic perspective.
Conclusion: In summary, our results indicate that OD has good prospects in the treatment of OS.
