Abstract 1631: Anti-cancer effects of vorinostat on 3D cultured pancreatic cancer cells

Abstract

Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers, often having a low survival rate mainly due to late diagnosis and limited therapies because of drug resistance. Treatment results shown in cell models used in studying various drugs often fail in clinical trials. The lack of translation of the effects observed in vitro to patients continues to halt progress. Genetic mutations are known in PDAC; however, recent studies have suggested the role of epigenetics in its initiation and progression to a malignant phenotype. Histone deacetylase (HDAC) proteins are highly expressed in a variety of cancers, including pancreatic cancer. Recent studies have shown that targeting these proteins through the use of HDAC inhibitors may be an effective therapy for pancreatic cancer. Using a 3D cultured pancreatic cell model, anti-cancer effects by vorinostat, a HDAC inhibitor, were investigated. Although both pancreatic cell lines, PANC-1 and Mia, contain mutated K-ras and P53, a differential effect in response to vorinostat was observed in expression of cancer genes using a Human Pancreatic Adenocarcinoma TagMan Array 96 (Applied Biosystems). In the PANC-1 cell model, vorinostat decreased expression of STAT6, which is known to play a role in migration and invasion. It also decreased significantly expression of insulin growth factor 1 (IGF1), IL-6, EGF, VEGFA and TGFB1. CCND2 and CCND2 were also downregulated. In contrast, Mia cell model showed decreased expression of EGF and IGF1, but no change with the other genes. These data suggest that vorinostat has effects on several potential pathways in pancreatic cancer possibly through epigenetic mechanisms that affect certain genes involved in progression and invasion. Currently, this drug in combination with other drugs is being investigated for pancreatic cancer. Citation Format: Fatemeh Nouri Emamzaden, Beverly Word, George Hammons, Beverly D. Lyn-Cook. Anti-cancer effects of vorinostat on 3D cultured pancreatic cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1631.