Antitumor effects of Mzs-1 from Chinese Artium lappa L. on HGC-27 cells via the PI3K/AKT/mTOR pathway in vitro and in vivo.

Abstract Background: Gastric cancer (GC), particularly at advanced stages, often results in therapeutic failure due to drug resistance and adverse effects. Traditional Chinese medicine (TCM), with its multi-target actions and favorable safety profile, presents a compelling alternative. Purpose: To evaluate the anti-tumor efficacy of Mzs-1, a synthetic analogue derived from Arctium lappa L., and elucidate its mechanism of action in gastric cancer. Study design: This study integrated computational prediction and experimental validation to evaluate the anti-tumor effects of Mzs-1 in vitro and in vivo. Methods: Network pharmacology analysis was conducted to identify the potential targets and pathways of Mzs-1, highlighting the PI3K/AKT/mTOR pathway. Molecular docking was performed to predict the binding affinity of Mzs-1 to key proteins in this pathway. Functional assays, including cell proliferation, apoptosis, and invasion, were performed in HGC-27 cells. Western blotting was used to examine the expression of PI3K/AKT/mTOR pathway components. In vivo efficacy was assessed in xenograft mouse models following Mzs-1 treatment. Results: In vitro, Mzs-1 suppressed HGC-27 cell proliferation and invasion while inducing apoptosis. These effects were enhanced by PI3K inhibition and attenuated by AKT activation. In vivo, Mzs-1 inhibited tumor growth and downregulated PI3K/AKT/mTOR signaling in xenograft tissues. Conclusion: Mzs-1 exerts anti-GC activity by modulating the PI3K/AKT/mTOR pathway, supporting its potential as a therapeutic candidate for gastric cancer.