Abstract 4959: Osteoprotegerin mediates resistance to TRAIL-induced apoptosis in pancreatic ductal adenocarcinoma

Abstract

Abstract [Purpose] Tumor Necrosis Factor (TNF)-Related Apoptosis-Inducing Ligand (TRAIL) has been shown to have great potential for the treatment of most human tumor cells without harming normal cells. However, some cancers show resistance to TRAIL induced apoptosis. The poor prognosis of both pancreatic ductal adenocarcinoma (PDAC) is likely due to the absence of valid approaches for early detection, the frequency of its metastases at the time of diagnosis, frequent recurrence after surgery, and poor responsiveness to chemotherapy. PDAC is also known as the most common resistant cells to TRAIL. Since osteoprotegerin (OPG) is known as a decoy receptor that binds to TRAIL and inhibits TRAIL-induced apoptosis, we hypothesized that OPG might play a role in mediating resistance to apoptosis in PDAC cells. [Methods and Results] To investigate the expression of OPG in PDAC cells, RT-PCR, Western blot and ELISA were performed. From the results, we found significant expression of OPG in both cell and cell culture medium. To investigate the apoptotic activity of TRAIL, we performed cell viability assay and apoptosis assay with or without siRNA against OPG. We found that PDAC cells showed significantly resistance to TRAIL induced apoptosis and knocking down of OPG sensitized TRAIL induced apoptosis in PDAC cells. [Conclusion] This study demonstrated that OPG played a role in resistance to TRAIL-induced apoptosis in PDAC cells. Expression of OPG might provide PDAC cells with an essential growth advantage through resistance to TRAIL-induced apoptosis. Inhibition of OPG expression and blocking OPG function might be a new therapeutic approach for the treatment of pancreatic cancer patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4959. doi:1538-7445.AM2012-4959