Anti-Lung Cancer Targets of Radix Paeoniae Rubra and Biological Molecular Mechanism: Network Pharmacological Analyses and Experimental Validation

Onco Targets Ther. 2021 Mar 16:14:1925-1936. doi: 10.2147/OTT.S261071. eCollection 2021.

Abstract

Objective: To systematically explore the pharmacological mechanism of Radix Paeoniae Rubra (RPR) against lung cancer (LC).

Methods: A network pharmacology approach, which involves active ingredients and target forecast, network construction, gene ontology and pathway enrichment, was employed in this research. In addition, the effect of Baicalein (BAI) in RPR on A549 cells was researched in vitro and in vivo.

Results: A total of 159 targets of the 29 active components in RPR were procured by pharmacokinetic parameters. The network analysis showed that β-sitosterol, baicalein, (+)-catechin, ellagic acid, stigmasterol, (2R, 3R)-4-methoxyl-distylin were the main ingredients and JUN, VEGFA, BCL2 were the hub targets of RPR in the treatment of LC. The functional enrichment analysis showed that RPR likely was useful to LC by regulating numerous pathways including Pathways in cancer, MAPK signaling pathway and so on. MTT results showed that 100μM, 200μM, 400μM of BAI had a time and dose-dependent inhibitory effect on A549 cells proliferation; Wound healing and transwell assays showed that 100μM, 200μM, 400μM of BAI could significantly restrain the migration and invasion of A549 cells; Flow cytometry assay results showed that 100μM, 200μM, 400μM of BAI could induce apoptosis of A549 cells. In vivo, BAI (50, 100 mg/kg) significantly inhibited tumor growth and promoted apoptosis of tumor cells compared with the control group.

Conclusion: BAI in RPR may exert anti-tumor effects by inhibiting the proliferation, migration and invasion of LC cells, and inducing the apoptosis of LC cells.

Keywords: baicalein; lung neoplasms; network pharmacology; radix paeoniae rubra.