Paeonol antagonizes oncogenesis of osteosarcoma by inhibiting the function of TLR4/MAPK/NF-κB pathway

Area of Science:

• Pharmacology
• Oncology
• Molecular Biology

Background:

• Paeonol (PAE), derived from Paeonia suffruticosa, exhibits potential anti-cancer properties.
• Osteosarcoma (OS) remains a significant challenge in oncology, necessitating novel therapeutic strategies.
• Understanding the molecular mechanisms of PAE in OS is crucial for its clinical application.

Purpose of the Study:

• To investigate the anti-osteosarcoma (OS) mechanism of paeonol (PAE).
• To elucidate the role of the Toll-like receptor 4 (TLR4)-mediated MAPK/NF-κB pathway in PAE's anti-OS effects.
• To validate the findings using in vitro and in vivo models.

Main Methods:

• Human OS cells were treated with varying concentrations of PAE to assess proliferation, apoptosis, and metastasis.
• The expression of TLR4 and the activity of the MAPK/NF-κB pathway were analyzed.
• TLR4 levels were manipulated to determine its role in PAE's efficacy.
• Xenograft mice models were used for in vivo validation.

Main Results:

• PAE suppressed OS cell proliferation and induced apoptosis in a dose-dependent manner.
• PAE inhibited OS cell migration and invasion, though not concentration-dependently.
• PAE deactivated the MAPK/NF-κB pathway and reduced TLR4 expression.
• Induced TLR4 expression diminished the anti-OS effects of PAE.
• PAE inhibited tumor growth and TLR4 expression in vivo.

Conclusions:

• The anti-osteosarcoma effects of PAE are mediated through the inhibition of TLR4 and its downstream MAPK/NF-κB signaling pathway.
• PAE demonstrates therapeutic potential for osteosarcoma treatment.
• Targeting the TLR4 pathway represents a viable strategy for enhancing PAE's anti-cancer activity.