In our previous work, we found that several canine and human osteosarcoma (OSA) cell lines, but not normal osteoblasts, exhibit constitutive phosphorylation of STAT3.
The inhibition of STAT3 in Saos-2 cells by siRNA or AG490 decreased cell proliferation, migration and invasion, down-regulated the mRNA expression of Cyclin D, Bcl-xL and Survivin and enhanced the apoptotic response.
Efficacy of the FLLL32 pharmacological inhibitor in delaying OS growth suggests that targeting JAK2/STAT3 may be a potential therapeutic strategy for patients with OS.
In addition, knockdown of LIF notably suppressed the proliferation and invasion of osteosarcoma via blocking the STAT3 signal pathway; in contrast, treatment with the recombinant LIF protein significantly promoted the growth and invasion of osteosarcoma through enhancing the phosphorylation of STAT3, which can be partially neutralized by the STAT3 inhibitor, HO-3867.
The findings demonstrated that ginkgetin exerts growth inhibitory and apoptotic effects on osteosarcoma cells through the inhibition of STAT3 and activation of caspase-3/9.
In addition, we detected the expression of vascular endothelial growth factor (VEGF) and signal transducer and activator of transcription 3 (STAT3) in osteosarcoma cell treated with Eag1 small interfering RNAs (siRNAs).
AK093407 is highly expressed in osteosarcoma cells and tissues, and promotes cell proliferation and viability and inhibits apoptosis of osteosarcoma cell line U-2OS via STAT3 activation.
In this study, we identify Toosendanin (TSN) is an effective inhibitor of STAT3, leading to the impediment of various oncogenic processes in osteosarcoma.
These results suggest that E2F1/DDR1/STAT3 pathway is critical for malignancy of osteosarcoma, which may provide a novel prognostic indicator or approach for osteosarcoma therapy.
MAX interactor 1, dimerization protein (MXI1), STAT3 and T-cell acute lymphocytic leukemia 1 (TAL1) were significant TFs enriched with target genes in OS samples.
Our findings provide information about the underlying mechanisms of miR-204/14-3-3ζ in OS cell proliferation through the STAT3 pathway, and suggest miR-204 and 14-3-3ζ as potential therapeutic targets in OS.