ASC-J9 Attenuates the Metastatic Potential of Oral Cancer Cells by Downregulating the STAT3/ITGB8 Signaling Pathway

Dimethylcurcumin (ASC-J9), a derivative of curcumin, has been reported to possess anticancer activity. However, its potential impact on oral squamous cell carcinoma (OSCC) has not been fully characterized. In this study, we aimed to determine whether ASC-J9 inhibits OSCC metastasis and to elucidate the molecular mechanisms involved. Our findings indicate that ASC-J9 treatment significantly reduced OSCC metastasis both in vitro and in vivo. Notably, ASC-J9 treatment led to a marked decrease in both mRNA and protein levels of integrin beta 8 (ITGB8) in OSCC cells. In addition, ASC-J9 suppresses epithelial-mesenchymal transition (EMT) through the upregulation of E-cadherin and the downregulation of vimentin, fibronectin, Snail, and Slug expression. Moreover, ASC-J9 treatment led to a reduction in phosphorylated STAT3 (p-STAT3) levels. Activation of STAT3 by the selective activator colivelin reversed the ASC-J9-induced suppression of ITGB8 expression and cell migration. These findings suggest that ASC-J9 inhibits ITGB8 in OSCC cells by blocking STAT3 activation, thereby reducing their invasive and migratory capabilities. Collectively, our results support ASC-J9 as a promising therapeutic candidate for the treatment of OSCC.