Abstract 2062: Inhibition of STAT3 overcomes gemcitabine resistance in pancreatic cancer cells

Abstract

Abstract Gemcitabine is used as the first line treatment of pancreatic ductal adenocarcinoma (PDAC), however, either innate or acquired resistance to gemcitabine limit its therapeutic efficacy. In this study, several DNA damage agents including DNA repair inhibitors, and kinase inhibitors were examined for suppression of cell growth of gemcitabine resistant cells. The results show that most of these compounds are cross-resistant to gemcitabine-resistant pancreatic cells. By using STRING protein network database, we found that STAT3 signaling pathway plays a connectional role to link targeted proteins we tested. Interestingly, gemcitabine-resistant pancreatic cells have higher level of phosphor-STAT3 (pSTAT3) and are more sensitive to STAT3 inhibitor, S3I-201. Furthermore, combined S3I-201 with gemcitabine synergically suppresses the growth of both cell lines in vitro. We also confirmed the therapeutic efficacy of combined treatments using xenografted model. Taken together, inhibition of STAT3 overcomes gemcitabine resistance in pancreatic cancer cells. This study may provide us with a new approach to treat pancreatic cancer as well as gemcitabine resistance of pancreatic cancer. Citation Format: Chi-Wei Chen, Ruiqin Wu, Yunxiao Meng, Wenge Zhu. Inhibition of STAT3 overcomes gemcitabine resistance in pancreatic cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2062. doi:10.1158/1538-7445.AM2017-2062