Abstract 4654: A novel proteasome inhibitor, bis-Benzylidine Piperidone (RA190), control hepatocellular carcinoma effectively through inhibiting STAT3

Abstract

Abstract Hepatocellular carcinoma(HCC) is one of the most common malignancy, especially in the HBV endemic Asia area. However, there is still lack of effective chemotherapy drug to treat HCC, expect Sorafenib, tyrosine kinase inhibitor, the only FDA approved chemotherapy drug to treat HCC. In this study, we explore the chemotherapeutic properties of a novel proteasome inhibitor, bis-Benzylidine Piperidone (RA190), and its ability to manipulate the tumor microenvironment. Unlike the marketed proteasome inhibitor Bortezomib, a chemotherapeutic drug used to treat relapsed multiple myeloma, which inhibits the 20S catalytic core of the 26S proteasome, RA190 irreversibly binds to the ubiquitin receptor RPN13/ADRM1 on the 19S regulatory cap of the 26S proteasome. RA190 inhibits proteasome function and triggers accumulation of polyubiquinated proteins, and has been shown to induce endoplasmic reticulum stress-related apoptosis in HepG2 and Hepa3B hepatoma cell lines. We also found RA190 We observed a significant apoptosis of cancer cells after treatment of RA190. These changes in cancer cell lines were caused by reduction of STAT3 activity. We also proved the treatment effect of RA190 in orthotropic HCC animal models. The initial study of this novel proteasome inhibitor demonstrates its potential as an effective HCC therapy. Citation Format: Rueyshyang Soong. A novel proteasome inhibitor, bis-Benzylidine Piperidone (RA190), control hepatocellular carcinoma effectively through inhibiting STAT3. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4654.