Pharmacogenomic analyzis of the responsiveness of gastrointestinal tumor cell lines to drug therapy: A transportome approach

• Published in: Pharmacological research 2016-11, Vol.113 (Pt A), p.364-375
• Main Authors: Grañé-Boladeras, Natàlia, Pérez-Torras, Sandra, Lozano, Juan José, Romero, Marta R., Mazo, Adela, Marín, José J.G., Pastor-Anglada, Marçal
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - pharmacology; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Proliferation - genetics; Digestive/gastrointestinal tumors; Gastrointestinal Neoplasms - drug therapy; Gastrointestinal Neoplasms - genetics; Gene Expression Regulation, Neoplastic - drug effects; Gene Expression Regulation, Neoplastic - genetics; Humans; Network; Nucleoside analogs; Nucleoside transporters; Pharmacogenetics - methods; RNA, Messenger - metabolism; Transportome
• ISSN: 1043-6618; 1096-1186
• DOI: 10.1016/j.phrs.2016.09.007

[Display omitted] In this study, we have addressed the pharmacogenomic basis of the response of gastrointestinal tumors to six anticancer drugs using a panel of fifteen cell lines derived from pancreatic, stomach and biliary tract cancers. We determined the constitutive expression levels of 96 genes, whose encoded proteins contribute to drug action, and identified a major gene network that contains broad selectivity nucleoside transporter genes, as well as several genes known to be involved in cell proliferation and survival. All cell lines were exposed to 5′-DFUR, 5-FU, gemcitabine, cisplatin, doxorubicin and paclitaxel for 48h and cell response was measured using MTT assays. We correlated the cell response of the fifteen cell lines with the mRNA expression of the selected 96 genes and identified sets of 4–5 genes whose expression profiles correlated to responsiveness to each anticancer drug. These genes may be good candidates as response predictors to such therapies.