Agrimonia pilosa Extract suppresses NSCLC growth through regulating PI3K/AKT/Bcl-2 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Agrimonia Pilosa is a traditional Chinese medicine with a long history, which is often used in clinic alone or in combined with other Chinese herb medicine to anti-inflammatory, hemostasis and treat many types cancers, including lung cancer. Agrimonia Pilosa Extract (APE) is extracted from the Agrimonia Pilosa. The potential molecular mechanism of APE on the non-small cell lung cancer remains unclear.

AIM OF THIS STUDY: The aim of this study was to investigate the molecular mechanism of APE induced apoptosis in NSCLC cells and its effect on metabolism.

MATERIALS AND METHODS: Constructed mouse transplantation tumor models to evaluate the anti-tumor effect of APE by pharmacodynamics test, histological staining and TUNEL staining. Analyzed alterations in metabolites and metabolic pathways in serum and tumor tissues from tumor-bearing mice by liquid chromatography-mass spectrometry (LC-MS)-based untargeted metabolomics. In addition, the key proteins and genes on the signaling pathway were verified by Western blotting (WB) and real-time fluorescence quantitative PCR(RT-qPCR) to reveal the anti-tumor mechanism of APE.

RESULTS: APE inhibited tumor growth by promoting apoptosis and caused metabolic changes. Specifically, they inhibited the PI3K/AKT/Bcl-2 signaling pathway while upregulating apoptotic markers such as TP53, Bax, Caspase-3, and Cytochrome c. Through metabolomics analysis of mouse serum and tumor tissue, 120 different metabolites were identified, including glutamate, PC(24:0/18:0), and LysoPE (18:0/0). Among these, 13 serum metabolites were down-regulated, 16 were up-regulated, 28 tumor metabolites were down-regulated, and 63 were up-regulated. Studies indicate that APE can regulate metabolic disorders associated with non-small cell lung cancer by influencing pathways like glycerophospholipid metabolism, amino acid metabolism, and the TCA cycle, thereby inducing cell apoptosis and leading to significant metabolic changes.

CONCLUSIONS: In this study, APE affected the apoptosis of non-small cell lung cancer cells by regulating the PI3K/AKT/Bcl-2 signal transduction pathway and various metabolic pathways thereby inhibited the growth of tumor cells.This deepened the understanding of the metabolic characteristics and apoptosis-related pathways in APE intervened NSCLC, and provided a reference for further research on the mechanism of action of its anticancer drugs.