Adenoviral-mediated overexpression of human equilibrative nucleoside transporter 1 (hENT1) enhances gemcitabine response in human pancreatic cancer |
| |
Authors: | Pérez-Torras Sandra García-Manteiga José Mercadé Elena Casado F Javier Carbó Neus Pastor-Anglada Marçal Mazo Adela |
| |
Affiliation: | Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, Spain. |
| |
Abstract: | Nucleoside-derived anticancer agents must be transported across the plasma membrane as a preliminary step to their conversion into active drugs. Hence, modulation of a specific nucleoside transporter may affect bioavailability and contribute significantly to sensitizing tumor cells to these anticancer agents. We have generated and functionally characterized a new recombinant adenovirus (Ad-hENT1) that has allowed us to overexpress the equilibrative nucleoside transporter hENT1 and to analyze its effects in human pancreatic tumor cells. Overexpression of hENT1 is associated with changes in cell cycle profile, in a variable manner depending on the particular cell type, thus suggesting a metabolic link between hENT1-mediated transport processes and the enzymatic machinery responsible for intracellular nucleoside metabolism. When assayed in vivo in a human pancreatic adenocarcinoma xenograft, intratumoral Ad-hENT1 injection improved the therapeutic response to gemcitabine. In summary, hENT1 overexpression is associated with alterations in nucleoside enzymatic machinery and cell cycle progression in cultured cells and enhances gemcitabine action in vivo. |
| |
Keywords: | hENT1 Adenovirus Nucleoside analogues Nucleoside transport Pancreatic cancer |
本文献已被 ScienceDirect PubMed 等数据库收录! |