Network pharmacology and experimental verification reveals the anti-growth and anti-migration roles of allicin in non-small cell lung cancer

Abstract

Allicin is considered to have anti-tumor activity in lung cancer (LC), but the underlying molecular mechanism remains unclear. This study aimed to evaluate the pharmacological mechanism of allicin against non-small cell lung cancer (NSCLC) using network pharmacological analysis and experimental validation. NSCLC cell lines (A549 and SK-MES-1) were treated with different concentrations of allicin. Cell proliferation, migration and apoptosis were determined using CCK8 assay, colony formation assay, transwell assay and flow cytometry. The potential targets of allicin and LC were screened using network pharmacology, and the 9 core targets with stable binding were molecular-docked with allicin. Functional and pathway enrichment analyses were performed using KEGG and GO analysis. The protein levels of p-EGFR/EGFR, p-PI3K/PI3K and p-AKT/AKT were analyzed using western blot. Allicin reduced NSCLC cell proliferation and migration, while inducing apoptosis in a dose-dependent manner. Network pharmacology and molecular docking were used to explore the potential molecular targets and pathways of allicin affecting LC progression. The results illustrated that EGFR, CASP3, NFKB1, SRC, PARP1, STAT1, MAPK3, MAPK14 and MCL1 were the core targets for the inhibitory effect of allicin on LC. Furthermore, KEGG and GO analysis showed that the anti-cancer role of allicin might be achieved by regulating EGFR/PI3K/AKT pathway. To further confirm this, WB was performed to explore the regulation of allicin on p-EGFR/EGFR, p-PI3K/PI3K and p-AKT/AKT protein levels, and the results confirmed that allicin inhibited the activity of EGFR/PI3K/AKT pathway to suppress NSCLC progression. Allicin restrained NSCLC cell growth and migration via inhibiting the EGFR/PI3K/AKT pathway, suggesting that allicin might be a promising therapeutic agent for NSCLC.