Study on the regulatory mechanism and experimental verification of icariin for the treatment of ovarian cancer based on network pharmacology

Ethnopharmacological relevance: Herba Epimedii (Berberidaceae) has the advantages of "nourishing the kidney and reinforcing the Yang". Many species in this genus have long been used in traditional Chinese medicine (TCM) and have been used as anticancer drugs in traditional Chinese herbal medicine formulations. Icariin, a major flavonoid glycoside extracted from Epimedium brevicornum Maxim, has been widely proven to exert an inhibitory effect on ovarian cancer (OC), and icariin can induce apoptosis and inhibit invasion and migration. However, the underlying mechanism remains unclear, so further research is necessary to verify its traditional use.

Aim of the study: This study aimed to explore the regulatory mechanism of icariin in the biological network and signalling pathway of OC through network pharmacology and cytological experiments.

Methods: Public databases and R × 3.6.2 software were adopted to predict the potential targets, construct the protein-protein interaction (PPI) network, and perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. After the network pharmacological analysis, cytological experiments, real-time quantitative PCR (qPCR) and Western blot (WB) analyses were used to verify the key signalling pathway.

Results: The targets related to treatment were TNF, MMP9, STAT3, PIK3CA, ERBB2, MTOR, IL2, PTGS2, KDR, and F2. GO and KEGG enrichment analyses indicated that various kinases and the PI3K/AKT signalling pathway were the most enriched molecules and pathways. Icariin inhibited OC SKOV3 cell proliferation, migration and invasion in vitro and promoted apoptosis by inhibiting the PI3K/AKT signalling pathway.

Conclusion: Icariin promotes apoptosis and suppresses SKOV3 cell activities through the PI3K-Akt signalling pathway. This research not only provides a theoretical and experimental basis for more in-depth studies but also offers an efficient method for the rational utilization of a series of icariin flavonoids as anti-tumour drugs.

Keywords: Cell apoptosis; ICA, Icariin; Network pharmacology; OC, Ovarian cancer; PI3K/AKT signal Pathway.