Luteolin alleviates lung cancer pain in mice by modulating AKT1

Abstract Objetives The treatment of lung cancer pain (LCP) faces the double challenge of high side effects of analgesics and unclear mechanisms. Luteolin (LUT), an active ingredient of Salvia miltiorrhiza Bge., has anti-tumor potential, but its mechanism in alleviating LCP has not been elucidated completely. To elucidate the molecular mechanism of LUT in alleviating LCP by modulating the AKT1. Methods Based on the network pharmacology strategy, potential active ingredients of Salvia miltiorrhiza Bge. and their targets for the treatment of LCP were collected from the TCMSP, HERB, and CTD databases. A protein-protein interaction (PPI) network was constructed in the STRING database to identify the hub genes. Detection of AKT1 expression was performed by RT-qPCR or western blot. The degree of pain in lung cancer patients was quantified using the Numeric Rating Scale (NRS). The CCK-8 and Transwell assays were used to assess human lung carcinoma epithelial cell (A549) viability and invasiveness. The sensitivity to pain in bone metastasis mice was assessed by measuring the mechanical paw withdrawal threshold. Results AKT1 had the highest node degree value in the PPI network. The clinical analysis showed that AKT1 expression level was positively correlated with LCP. Cellular experiments showed that LUT concentration-dependently inhibited the cell viability of A549 cells and hindered cell invasion by down-regulating AKT1. The in vivo experiments showed that LUT treatment alleviated the pain of bone metastasis mice and decreased AKT1 expression. Conclusions LUT suppressed lung cancer cell invasion and relieved LCP through AKT1 inhibition.