Objective  To investigate the relationship between the inhibition of hS100A6 on osteosarcoma cell lines MG63 and U2OS and Wnt/ β - catenin signaling pathway. Methods Adenoviruses carrying human β - catenin and its siRNA gene respectively were used to up - regulate and down - regulate the expression of β- catenin in MG63 and U2OS cells. Then MTT assay

Hoechst staining

scratching test and Transwell assay were used to detect cells proliferation

apoptosis and migration

respectively after the treatment of hS10

0A6. Results Ad β - catenin and AdSi β - catenin up - and down - regulated β - catenin expression in MG63 and U2OS (

P

0.05)

respectively. Exogenous hS100A6 inhibited the proliferation of wild osteosarcoma cell lines MG63 and U2OS (

P

0 . 05)

while over - or low - expression of β - catenin reduced or enhanced the inhibitive effect of S100A6 on cell proliferation respectively (

P

0 . 05). Exogenous hS100A6 promoted the apoptosis of 2 wild cell lines (

P

0 . 05)

but over- or low-expression of β - catenin enhanced or reduced the ability of hS100A6 respectively (

P

0 . 05). Exogenous hS100A6 inhibited the migration of MG63 cells

however

over- or low-expression of β - catenin reduced or enhanced the ability of hS100A6 to inhibit migration (

P

0 . 05). Conclusion The inhibitory role of hS100A6 on osteosarcoma cells is regulated negatively by β - atenin. This inhibitory role may be controlled by Wnt/ β- atenin and other signaling pathways.