Adenoviral-mediated overexpression of human equilibrative nucleoside transporter 1 (hENT1) enhances gemcitabine response in human pancreatic cancer
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 anticanc...
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| Veröffentlicht in: | Biochemical pharmacology 2008-08, Vol.76 (3), p.322-329 |
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| creator | Pérez-Torras, Sandra García-Manteiga, José Mercadé, Elena Casado, F. Javier Carbó, Neus Pastor-Anglada, Marçal Mazo, Adela |
| description | 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. |
| doi_str_mv | 10.1016/j.bcp.2008.05.011 |
| format | Article |
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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
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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.</description><subject>Adenocarcinoma - drug therapy</subject><subject>Adenocarcinoma - metabolism</subject><subject>Adenocarcinoma - pathology</subject><subject>Adenoviridae - genetics</subject><subject>Adenovirus</subject><subject>Animals</subject><subject>Antimetabolites, Antineoplastic - pharmacology</subject><subject>Antimetabolites, Antineoplastic - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Cell Cycle - drug effects</subject><subject>Cell Line, Tumor</subject><subject>Cell Survival - drug effects</subject><subject>Deoxycytidine - analogs & derivatives</subject><subject>Deoxycytidine - pharmacology</subject><subject>Deoxycytidine - therapeutic use</subject><subject>Equilibrative Nucleoside Transporter 1 - biosynthesis</subject><subject>Equilibrative Nucleoside Transporter 1 - genetics</subject><subject>Female</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Genetic Vectors</subject><subject>hENT1</subject><subject>Humans</subject><subject>Injections, Intralesional</subject><subject>Liver. Biliary tract. Portal circulation. Exocrine pancreas</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>Neoplasm Transplantation</subject><subject>Nucleoside analogues</subject><subject>Nucleoside transport</subject><subject>Pancreatic cancer</subject><subject>Pancreatic Neoplasms - drug therapy</subject><subject>Pancreatic Neoplasms - metabolism</subject><subject>Pancreatic Neoplasms - pathology</subject><subject>Pharmacology. Drug treatments</subject><subject>Protein Biosynthesis - drug effects</subject><subject>Protein Biosynthesis - genetics</subject><subject>Recombinant Fusion Proteins - administration & dosage</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Tumors</subject><subject>Uridine - metabolism</subject><subject>Xenograft Model Antitumor Assays</subject><issn>0006-2952</issn><issn>1873-2968</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU1v1DAQhi0EotvCD-CCfAHBIcHjfKwjTlXVAlIFl3K2nPGE9Sprp3aygt_BH8arjeDGyWPpmUej92XsFYgSBLQf9mWPUymFUKVoSgHwhG1AbatCdq16yjZCiDbPjbxglyntT1_VwnN2AapRXS3khv2-tuTD0UUzFgeyzsxkeThSpJ9TpJRc8DwMfLccjOf0uLjR9dHM7kjcLzhSSM4Sn6PxaQpxpsiBv9vdfn2A95z8znikxH_QAd1seueJZ-kUfCLu_GqdMhQpO5HjiY8v2LPBjIleru8V-353-3Dzubj_9unLzfV9gTXIueixsaZRwlY4dKZDqusBpGwrUgYsiVY2UHdVTdK2HYpGDk21NVgjtQSDqqsr9vbsnWJ4XCjN-uAS0jgaT2FJGrptp9qqyyCcQYwhpUiDnqI7mPhLg9CnJvRe5yb0qQktGp2byDuvV_nS52D_bazRZ-DNCpiEZhxyhOjSX07mgxVIkbmPZ45yFEdHUSd0lHOyLhLO2gb3nzP-APciqWg</recordid><startdate>20080801</startdate><enddate>20080801</enddate><creator>Pérez-Torras, Sandra</creator><creator>García-Manteiga, José</creator><creator>Mercadé, Elena</creator><creator>Casado, F. 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Drug treatments</topic><topic>Protein Biosynthesis - drug effects</topic><topic>Protein Biosynthesis - genetics</topic><topic>Recombinant Fusion Proteins - administration & dosage</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Tumors</topic><topic>Uridine - metabolism</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pérez-Torras, Sandra</creatorcontrib><creatorcontrib>García-Manteiga, José</creatorcontrib><creatorcontrib>Mercadé, Elena</creatorcontrib><creatorcontrib>Casado, F. 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Javier</au><au>Carbó, Neus</au><au>Pastor-Anglada, Marçal</au><au>Mazo, Adela</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Adenoviral-mediated overexpression of human equilibrative nucleoside transporter 1 (hENT1) enhances gemcitabine response in human pancreatic cancer</atitle><jtitle>Biochemical pharmacology</jtitle><addtitle>Biochem Pharmacol</addtitle><date>2008-08-01</date><risdate>2008</risdate><volume>76</volume><issue>3</issue><spage>322</spage><epage>329</epage><pages>322-329</pages><issn>0006-2952</issn><eissn>1873-2968</eissn><coden>BCPCA6</coden><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.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>18589402</pmid><doi>10.1016/j.bcp.2008.05.011</doi><tpages>8</tpages></addata></record> |
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| subjects | Adenocarcinoma - drug therapy Adenocarcinoma - metabolism Adenocarcinoma - pathology Adenoviridae - genetics Adenovirus Animals Antimetabolites, Antineoplastic - pharmacology Antimetabolites, Antineoplastic - therapeutic use Biological and medical sciences Cell Cycle - drug effects Cell Line, Tumor Cell Survival - drug effects Deoxycytidine - analogs & derivatives Deoxycytidine - pharmacology Deoxycytidine - therapeutic use Equilibrative Nucleoside Transporter 1 - biosynthesis Equilibrative Nucleoside Transporter 1 - genetics Female Gastroenterology. Liver. Pancreas. Abdomen Genetic Vectors hENT1 Humans Injections, Intralesional Liver. Biliary tract. Portal circulation. Exocrine pancreas Medical sciences Mice Mice, Inbred BALB C Mice, Nude Neoplasm Transplantation Nucleoside analogues Nucleoside transport Pancreatic cancer Pancreatic Neoplasms - drug therapy Pancreatic Neoplasms - metabolism Pancreatic Neoplasms - pathology Pharmacology. Drug treatments Protein Biosynthesis - drug effects Protein Biosynthesis - genetics Recombinant Fusion Proteins - administration & dosage Reverse Transcriptase Polymerase Chain Reaction Tumors Uridine - metabolism Xenograft Model Antitumor Assays |
| title | Adenoviral-mediated overexpression of human equilibrative nucleoside transporter 1 (hENT1) enhances gemcitabine response in human pancreatic cancer |
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