Timosaponin AIII (TSAIII) is a steroidal
saponin which demonstrates anti-tumour activities. However, the effect of TSAIII on human
osteosarcoma cells remains largely unknown. In this study, we demonstrated that TSAIII exerted a significant inhibitory effect on the distribution of cytoskeletal
F-actin and cytoskeletal-related
proteins, which contributed to the suppression of cell migration and invasion, without inhibiting cell growth or apoptosis. In the synergistic inhibitory analysis, cotreatment of TSAIII with αVβ3
integrin inhibitor [Cyclo(RGDyK)] or
focal adhesion kinase (FAK) inhibitor (PF-573228) exerted greater synergistic inhibitory effects on the expression of Intergin αVβ3/FAK/
cofilin axis, thus inhibiting the migration and invasion capacities of human
osteosarcoma cells. TSAIII was demonstrated to significantly inhibit the pulmonary
metastasis formation of human
osteosarcoma cells in vivo in
metastasis animal models. These findings reveal the inhibitory effects of TSAIII on the
metastasis progression of human
osteosarcoma cells and the regulation of integrin-αVβ3-FAK-Src and TESK1/p-
cofilin mediated cytoskeletal
F-actin pathway. Therefore, TSAIII might represent a novel strategy for the auxiliary treatment of human
osteosarcoma cells.