Title:Network Pharmacology-based Prediction and Verification of Shikonin for Treating Colorectal Cancer
Volume: 17
Issue: 3
Author(s): Zefeng Wang, Qianfei Cui, Ling Shi, Meiling Zhang, Peng Song*, Dongzhu Duan*Wenjing Guo*
Affiliation:
- Affiliated Hospital of Gansu University of Chinese Medicine, , Lanzhou , 730000, China
- Research Center of Traditional Chinese Medicine, Gansu Province, Gansu University of Chinese Medicine, Lanzhou,
730000, China
- Key Laboratory of Prevention and Treatment of Chronic Diseases by TCM in Gansu Province, Affiliated
Hospital of Gansu University of Chinese Medicine, Lanzhou, 730000, China
- Shanxi Key Laboratory of Phytochemistry
and College of Chemistry & Chemical Engineering, Baoji University of Arts and Sciences, Baoji, 721013,
China
- Research Center of Traditional Chinese Medicine, Gansu Province, Gansu University of Chinese Medicine, Lanzhou,
730000, China
Keywords:
Shikonin, colorectal cancer, network pharmacology, target analysis, molecular docking, cell experiments, signaling pathway.
Abstract:
Background: Shikonin (SKN), a naturally occurring naphthoquinone, is a major active
chemical component isolated from Lithospermum erythrorhizon Sieb Zucc, Arnebia euchroma
(Royle) Johnst, or Arnebia guttata Bunge, and commonly used to treat viral infection, inflammation,
and cancer. However, its underlying mechanism has not been elucidated.
Objective: This study aims to explore the antitumor mechanism of SKN in colorectal cancer (CRC)
through network pharmacology and cell experiments.
Methods: SymMap database and Genecards were used to predict the potential targets of SKN and
CRC, while the cotargets were obtained by Venn diagram. The cotargets were imported into the
website of String and DAVID, constructing the protein-protein interaction (PPI) network, performing
Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment
analyses, the Compound-Target-Pathway (C-T-P) network was generated by connecting potential
pathways with the corresponding targets.
Results: According to the results of network pharmacological analysis, the cell experiments were
used to verify the key signal pathway. The most relevant target of SKN for the treatment of CRC
was PI3K/Akt signaling pathway. SKN inhibited CRC cells (HT29 and HCT116) proliferation, migration,
and invasion, and promoted cell apoptosis by targeting IL6 and inhibiting the
IL6R/PI3K/Akt signaling pathway. SKN promotes apoptosis and suppresses CRC cells’ (HT29
and HCT116) activity through the PI3K-Akt signaling pathway.
Conclusion: This research not only provided a theoretical and experimental basis for more in-
-depth studies but also offered an efficient method for the rational utilization of a series of Traditional
Chinese medicines as anti-CRC drugs.
