A new signal transducer and activator of transcription 3 inhibitor, BBI608, in malignant mesothelioma cell lines
Chronic inflammation plays a key role in the pathogenesis of malignant pleural mesothelioma as a result of asbestos exposure. Signal transducer and activator of transcription 3 (STAT3) signaling is a major pathway for cancer inflammation. The purpose of this study was to investigate the effectiveness of a new STAT3 inhibitor, BBI608, on mesothelioma cells in vitro and in vivo . The results showed that BBI608 blocked STAT3 phosphorylation, with and without suppression of IL-6. The effects of BBI608 on STAT3 downstream target genes such as cyclin D1 and survivin involved a decrease in cell viability with induction of apoptosis and cell cycle arrest. Nuclear translocation of phosphorylated STAT3 was blocked by BBI608. In addition, the agent showed significant antitumor activity in xenograft mouse models implanted with mesothelioma cells. These findings suggest that BBI608 may be a novel agent for malignant mesothelioma.