WITHDRAWN: Anti-lung cancer mechanism of Hedyotis diffusa Willd based on network pharmacology and molecular docking

Background: Lung cancer has the highest mortality rate among all cancer types. Traditional Chinese medicines with heat clearing and detoxification efficacy have been extensively studied for the treatment of lung cancer. However, the inhibitory effect of Hedyotis diffusa Willd (HDW), with heat clearing and detoxification efficacy, on lung cancer and the underlying mechanism remain unclear. Objective: To explore the potential mechanism of action of HDW in the treatment of lung cancer based on network pharmacology and molecular docking techniques. Methods: The pharmacological database of the traditional Chinese medicine system and the analysis platform (TCMSP) were used to search for the active components and targets of HDW. Disease targets were collected using the GeneCard and OMIM databases. Construction of “active ingredient-target-disease” and protein interaction (PPI) networks was performed using Cytoscape Software and the STRING Database. GO (gene ontology) and KEGG (Kyoto Encyclopaedia of Genes and Genomes) enrichment analyses were carried out using the R language, and visualisation was performed. Finally, Molecular docking was performed between the bioactive components and core targets. The molecular mechanism underlying the effects of Hedyotis diffusa injection (HDI) treatment on lung cancer was verified in vitro and in vivo by culturing lung cancer A549 cells. Results: The “active ingredient-target-disease” network screened five core active components of HDW; the PPI network screened 23 core targets. Through enrichment analyses, it was found that the mechanism of action mainly involved PI3K/AKT signaling pathways. Molecular docking results showed that the main active components and the core target could strongly associate. In vitro experimental results showed that HDI inhibited the proliferation of A549 lung cancer cells and can regulate apoptosis of lung cancer A549 cells through PI3K / Akt signaling pathway. The results based on tumour-bearing nude mice showed that HDI could significantly reduce the volumes and weights of tumours without affecting the body weight and no significant toxic effects and that HDI significantly increased tumour tissue cell apoptosis. Conclusion: This study revealed the mechanism through which HDW affects lung cancer through multi-component-multi-target-multi-pathway means and provides a scientific basis and research ideas for follow-up studies on HDW for the treatment of lung cancer.