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

As the the major functional component of Paeonia suffruticosa, paeonol (PAE) has shown its potential to inhibit the progression of multiple cancer types. In the current study, the mechanism driving the effect of PAE on osteosarcoma (OS) was investigated by focusing on its influence on TLR4-mediated MAPK/NF-κB pathway. Human OS cells were firstly administrated with PAE of different concentrations to assess its effect on the proliferation, apoptosis, metastasis, and TLR4/MAPK/NF-κB pathway in OS cells. Thereafter, the level of TLR4 was induced in OS cells before PAE administration to explore the role of the molecule in the anti-OS function of PAE. The results of in vitro assays were further validated with xenograft mice models. The administration of PAE of two doses both suppressed the proliferation and induced apoptosis in OS cells in a dose-dependent manner. Regarding the effect on the metastasis potential of OS cells, PAE inhibited the migration and invasion potential of the cells, but the effect did not change with concentrations. The administration of PAE also inhibited the expression of TLR4 and deactivated MAPK/NF-κB pathway. Moreover, the induced expression of TLR4 counteracted the anti-OS function of PAE. Further validation with xenograft models also showed that PAE inhibited solid tumor growth and TLR4 expression in OS mice. In conclusion, it was inferred that the anti-OS function of PAE depended on the inhibition of TLR4 and its downstream MAPK/NF-κB pathway.