Network pharmacology reveals that Yanghe Decoction inhibits osteosarcoma progression via ROS-induced mitochondrial dysfunction and enhances cisplatin sensitivityOA
Osteosarcoma(OS)is a highly aggressive bone malignancy with limited treatment options and frequent chemoresistance,Yanghe Decoction(YHD),a traditional Chinese medicine formula,has demonstrated anti-tumor potential,but its mechanisms in OS remain unclear,In this study,we employed a network pharmacology approach to identify 67 active components and 101 OS-related targets of YHD,with core targets including AKT1,TP53,MAPK14,and CASP3,mainly enriched in the PI3K/AKT and MAPK signaling pathways,Molecular docking confirmed strong binding affinities between representative compounds and these targets,Functional experiments revealed that YHD inhibited OS cell proliferation,migration,and invasion,and promoted apoptosis by elevating intracellular reactive oxygen species levels and inducing mitochondrial dysfunction,Mechanistically,YHD suppressed the PI3K/AKT pathway while activating p38 MAPK signaling,Importantly,YHD enhanced the sensitivity of OS cells to cisplatin,demonstrating a synergistic inhibitory effect in vitro and in an orthotopic OS mouse model,These findings suggest that YHD exerts its anti-osteosarcoma effects via reactive oxygen species-mediated mitochondrial disruption and pathway modulation,and may serve as a promising adjuvant to conventional chemotherapy.
Yanran Huang;Dagang Tang;Runhan Zhao;Jun Zhang;Xiao Qu;Ningdao Li;Yi Ren;Xiaoji Luo
Department of Orthopaedic Surgery,Chongqing Municipal Health Commission Key Laboratory of Musculoskeletal Regeneration and Translational Medicine/Orthopaedic Research Laboratory,The First Affiliated Hospital of Chongqing Medical University,Chongqing 400016,ChinaDepartment of Orthopaedic Surgery,Chongqing Municipal Health Commission Key Laboratory of Musculoskeletal Regeneration and Translational Medicine/Orthopaedic Research Laboratory,The First Affiliated Hospital of Chongqing Medical University,Chongqing 400016,ChinaDepartment of Orthopaedic Surgery,Chongqing Municipal Health Commission Key Laboratory of Musculoskeletal Regeneration and Translational Medicine/Orthopaedic Research Laboratory,The First Affiliated Hospital of Chongqing Medical University,Chongqing 400016,ChinaDepartment of Orthopaedic Surgery,Chongqing Municipal Health Commission Key Laboratory of Musculoskeletal Regeneration and Translational Medicine/Orthopaedic Research Laboratory,The First Affiliated Hospital of Chongqing Medical University,Chongqing 400016,ChinaDepartment of Orthopaedic Surgery,Chongqing Municipal Health Commission Key Laboratory of Musculoskeletal Regeneration and Translational Medicine/Orthopaedic Research Laboratory,The First Affiliated Hospital of Chongqing Medical University,Chongqing 400016,ChinaDepartment of Orthopaedic Surgery,Chongqing Municipal Health Commission Key Laboratory of Musculoskeletal Regeneration and Translational Medicine/Orthopaedic Research Laboratory,The First Affiliated Hospital of Chongqing Medical University,Chongqing 400016,ChinaChongqing Hospital of Traditional Chinese Medicine,Chongqing 400011,ChinaDepartment of Orthopaedic Surgery,Chongqing Municipal Health Commission Key Laboratory of Musculoskeletal Regeneration and Translational Medicine/Orthopaedic Research Laboratory,The First Affiliated Hospital of Chongqing Medical University,Chongqing 400016,China Chongqing General Hospital,Chongqing University,Chongqing,401147,China
医药卫生
Mitochondrial functionOsteosarcomaP38PI3K/AKTYanghe decoction
《Genes & Diseases》 2026 (3)
P.617-633,17
supported by the First Affiliated Hospital of Chongqing Medical University''s"Discipline Summit Plan"(Chongqing,China)(No.cyyy-xkdfjhcgzh-202303)Chongqing Young and Middle-aged Medical High-end Talent Studio(China)(No.cstc2022ycjh-bgzxm0103)the Science and Technology Research Program of Chongqing Municipal Education Commission(China)(No.KJZD-M202402802)the Horizontal Scientific Research Project of the First Affiliated Hospital of Chongqing Medical and Pharmaceutical College(Chongqing Medical and Pharmaceutical College Of China)(No.2025YGZKY01).
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