We recently demonstrated that heat shock protein 90 (HSP90) is involved in the regulation of runt-related transcription factor 2 via the AKT/GSK-3β/β-catenin signaling pathway in OS.
The expression of Wnt3α and p-GSK-3β were also significantly upregulated indicating that the Wnt/β-catenin signaling pathway was activated during the EMT of osteosarcoma driven by BMP-2.
PP2A was a direct target of miR-21, which participated in the effects of ASBEL and miR-21 on the activation of phosphatidylinositol 3-kinase/protein kinase 3/glycogen synthase kinase-3β (PI3K/AKT/GSK3β) and mitogen-activated protein kinase/extracellular regulated protein kinase (MEK/ERK) signaling pathways as well as the enhancement of osteosarcoma cell proliferation, migration, and invasion.
PPI induced inhibition of osteosarcoma cell viability was abolished upon addition of GSK-3β specific inhibitor, CHIR99021, while PPI induced inhibition of osteosarcoma cell viability and migration were potentiated by β-catenin silencing.
Inhibition of GSK-3β activity by pharmacological inhibitors or of its expression by RNA interference suppressed proliferation of osteosarcoma cells and induced apoptosis.
Knockdown of TRPM8 by siRNA in osteosarcoma cells leads to the impaired regulation of intracellular Ca(2+) concentration and then the Akt-GSK-3β pathway and the phosphorylation of p44/p42 and FAK are suppressed.
Celecoxib inhibited MG-63 cell viability, possibly by activating GSK-3β and inhibiting β-catenin-dependent gene transcription, suggesting a role for celecoxib in osteosarcoma treatment.