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Cytotoxic Efficacy of Photodynamic Therapy in Osteosarcoma Cells In Vitro
Published on: March 18, 2014
Network pharmacology reveals that Yanghe Decoction inhibits osteosarcoma progression via ROS-induced mitochondrial
Yanran Huang1, Dagang Tang1, Runhan Zhao1
1Department 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.
Abstract:
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.
Insights
Yanghe Decoction (YHD) shows anti-osteosarcoma potential by disrupting mitochondria and modulating signaling pathways. It enhances cisplatin sensitivity, offering a promising adjuvant therapy for bone cancer.
Area of Science:
- Oncology
- Pharmacology
- Traditional Chinese Medicine
Background:
- Osteosarcoma (OS) is an aggressive bone cancer with poor treatment outcomes.
- Chemoresistance is a major challenge in osteosarcoma management.
- The anti-tumor mechanisms of Yanghe Decoction (YHD) in OS are not well understood.
Purpose of the Study:
- To investigate the anti-osteosarcoma mechanisms of YHD using network pharmacology and experimental validation.
- To identify active components and molecular targets of YHD in osteosarcoma.
- To evaluate YHD's potential as an adjuvant therapy for osteosarcoma.
Main Methods:
- Network pharmacology identified YHD components and targets.
- Molecular docking assessed compound-target interactions.
- In vitro assays evaluated YHD's effects on OS cell proliferation, migration, invasion, and apoptosis.
- Western blotting analyzed key signaling pathways (PI3K/AKT, MAPK).
- In vivo studies assessed YHD's efficacy in an orthotopic OS mouse model.
Main Results:
- YHD targets 101 OS-related genes, with AKT1, TP53, MAPK14, and CASP3 as core targets.
- YHD inhibited OS cell proliferation, migration, and invasion, while promoting apoptosis.
- YHD induced mitochondrial dysfunction and elevated reactive oxygen species (ROS).
- YHD suppressed PI3K/AKT signaling and activated p38 MAPK signaling.
- YHD enhanced cisplatin sensitivity in OS cells both in vitro and in vivo.
Conclusions:
- YHD exerts anti-osteosarcoma effects through ROS-mediated mitochondrial disruption and modulation of PI3K/AKT and MAPK pathways.
- YHD demonstrates potential as an adjuvant therapy to improve conventional chemotherapy efficacy for osteosarcoma.
- Further research into YHD's active compounds and precise mechanisms is warranted.
