Open Access

ARTICLE

Integrated Network Pharmacology and Molecular Docking to Reveal the Mechanism of Tetrandrine in Tumor Chemoresistance

by Xuehua Luo^1,#, Huijun Xie^2,#, Li Han¹, Qiaoming Zhong³, Meng Xu^4,*, Ling Jin^1,*

1 Department of Traditional Chinese Medicine, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China
2 College of Traditional Chinese Medicine of Jinan University, Guangzhou, 510632, China
3 Luogang Street Community Health Service Center, Guangzhou, 510525, China
4 Department of Oncology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China

* Corresponding Authors: Meng Xu. Email: ; Ling Jin. Email:
# These authors contributed equally to this work

Oncologie 2021, 23(3), 425-438. https://doi.org/10.32604/Oncologie.2021.017267

Received 27 April 2021; Accepted 28 June 2021; Issue published 26 September 2021

Abstract

Tetrandrine has a variety of anti-tumor effects including against or reversal of tumor chemoresistance, but its mechanism of against tumor chemoresistance is still unclear. Therefore, the analytical method of network pharmacology and molecular docking was used to investigate the mechanism by which tetrandrine acts in tumor chemoresistance. We used public databases (PubChem, SwissADEM, SwissTargetPrediction) to obtain the physicochemical information and targets of tetrandrine, and used gene databases (GeneCards and OMIM) to collected disease targets, respectively. The intersection targets of disease and drug were analyzed by RStudio. We built protein-protein interaction network through the STRING database, and used Cystoscope to screen out hub genes. GO and KEGG pathway enrichment analysis were analyzed by Metascape database and RStudio. “Component-target-pathway” network was erected by Cystoscope. Ultimately, the key targets were chosen to dock with tetrandrine via molecular docking to verify network analysis results. 29 common targets were screened out through intersection. AKT1, PIK3CA, PIK3CB, PIK3CG, JAK2, IGF1R, KDR, SRC and MTOR were the core targets. KEGG pathway enrichment mainly included PI3K-AKT signaling pathway, EGFR tyrosine kinase inhibitor resistance, and Rap1 signaling pathway. Molecular docking indicated that the configuration of protein binding of ligand is stable. In conclusion, the against tumor chemoresistance effect of tetrandrine has the characteristics of multiple targets and multiple pathways, and the prediction of network pharmacology and molecular docking indicated that MTOR, SRC, PIK3CA were the key targets of tetrandrine in tumor chemoresistance, which provides a scientific basis for subsequent research on its anti-tumor chemoresistance mechanism.

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