Cancers
Matrine Suppresses Osteosarcoma Lung Metastasis by Targeting the PI3K/AKT Signaling Pathway to Induce Mitochondrial Dysfunction
By Chanyi Jiang, Xiankun Liu, Yijun Yu and 4 others.
Abstract
Objective
Osteosarcoma, the most common primary bone malignancy in children and adolescents, frequently metastasizes to the lung, with a five-year survival rate of about 20% after lung metastasis. This study assessed whether matrine suppresses osteosarcoma lung metastasis by inducing mitochondrial dysfunction through inhibition of the PI3K/AKT pathway.
Methods
Using 143B, U2OS, and MG63 cells, we assessed proliferation, colony formation, and invasion; examined mitochondrial ultrastructure, membrane potential, and reactive oxygen species (ROS); and measured PI3K/AKT phosphorylation and mitochondrial dynamics and apoptosis-related proteins by Western blotting. Direct binding of matrine to PI3K was verified by molecular docking and surface plasmon resonance (SPR). Rescue experiments used the PI3K agonist 740 Y-P, and efficacy was tested in subcutaneous xenograft and tail vein lung metastasis models.