RNA-seq of combinatory treatment of gemcitabine+UVI5008 and gemcitabine+MS275 in human pancreatic adenocarcinoma human cell lines

Epigenetic modifications could drive some of the molecular events implicated in proliferation, drug resistance and metastasis of pancreatic ductal adenocarcinoma (PDAC). Thus, epigenetic enzyme inhibitors could be the key to revert those events and transform PDAC into a drug-sensitive tumor.We have performed a systematic study with two different epigenetic enzyme inhibitors (UVI5008, MS275) targeting either Histone Deacetylase 17 (HDAC) 1 or 1/4, DNA methyltransferase 3a (DNMT3a), Euchromatic histone lysine methyltrans- 18 ferase 2 (EHMT2) or Sirtuin 1 (SIRT1), and one drug that restores the p53 function (P53R3), in three 19 different human PDAC cell lines (MIA PaCa-2 and BxPC-3). The synergistic effect of these antitumoral drugs with gemcitabine was tested and the most efficient combinations were characterized by RNA-seq. The combination of UVI5008 or MS275 with gemcitabine induced a synergistic effect at low concentration and the RNA-Seq analysis revealed some synergy candidate genes as potential biomarkers.