STAT3 as a target of molecular targeting therapy for oral cancer: Cell-based screening using inhibitor screening kits

Abstract

Molecular targeting therapy has recently received attention owing to its high specificity for cancer cells; numerous researchers have been working to identify novel target molecules. In this study, we attempted to identify new targets through cell-based screening with inhibitor panel kits. The growth-inhibitory effects of inhibitors from the Screening Committee of Anticancer Drugs inhibitor kits, which contain 173 chemical inhibitors, were evaluated in oral squamous-cell carcinoma (OSCC) cell lines. Some of the inhibitors strongly suppressed the proliferation of OSCC cells. Of these inhibitors, we chose JSI-124, a specific inhibitor of STAT3, to investigate further. JSI-124 significantly inhibited the growth of OSCC cell lines and then induced DNA fragmentation, poly (ADP-ribose) polymerase cleavage, and caspase 3 activation in a dose-dependent manner. Treatment with JSI-124 resulted in a decrease of phosphorylated STAT3 and a downregulated expression of survivin, a downstream molecule of the STAT3 signaling cascade. Our data suggest that inhibition of STAT3 signaling by JSI-124 might be promising as a molecular therapy strategy against OSCC.