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

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.

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

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.

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.

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.