AUTHOR=Zhang Lingling , Gong Yanju , Zhang Lei , Liang Bing , Xu Huan , Hu Wangming , Jin Zhong , Wu Xiao , Chen Xiongbin , Li Min , Shi Liangqin , Shi Yaping , Li Mingjian , Huang Yong , Wang Yong , Yang Lan TITLE=Gou Qi Zi inhibits proliferation and induces apoptosis through the PI3K/AKT1 signaling pathway in non-small cell lung cancer JOURNAL=Frontiers in Oncology VOLUME=12 YEAR=2022 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.1034750 DOI=10.3389/fonc.2022.1034750 ISSN=2234-943X ABSTRACT=Background

Gou Qi Zi (Lycium barbarum) is a traditional herbal medicine with antioxidative effects. Although Gou Qi Zi has been used to prevent premature aging and in the treatment of non-small cell lung cancer (NSCLC), its mechanism of action in NSCLC remains unclear. The present study utilized network pharmacology to assess the potential mechanism of action of Gou Qi Zi in the treatment of NSCLC.

Methods

The TCMSP, TCMID, SwissTargetPrediction, DrugBank, DisGeNET, GeneCards, OMIM and TTD databases were searched for the active components of Gou Qi Zi and their potential therapeutic targets in NSCLC. Protein-protein interaction networks were identified and the interactions of target proteins were analyzed. Involved pathways were determined by GO enrichment and KEGG pathway analyses using the Metascape database, and molecular docking technology was used to study the interactions between active compounds and potential targets. These results were verified by cell counting kit-8 assays, BrdU labeling, flow cytometry, immunohistochemistry, western blotting, and qRT-PCR.

Results

Database searches identified 33 active components in Gou Qi Zi, 199 predicted biological targets and 113 NSCLC-related targets. A network of targets of traditional Chinese medicine compounds and potential targets of Gou Qi Zi in NSCLC was constructed. GO enrichment analysis showed that Gou Qi Zi targeting of NSCLC was mainly due to the effect of its associated lipopolysaccharide. KEGG pathway analysis showed that Gou Qi Zi acted mainly through the PI3K/AKT1 signaling pathway in the treatment of NSCLC. Molecular docking experiments showed that the bioactive compounds of Gou Qi Zi could bind to AKT1, C-MYC and TP53. These results were verified by experimental assays.

Conclusion

Gou Qi Zi induces apoptosis and inhibits proliferation of NSCLC in vitro and in vivo by inhibiting the PI3K/AKT1 signaling pathway.