Abstract | BACKGROUND & AIMS: METHODS: We evaluated proliferation and apoptosis of human pancreatic cancer cells (PANC-1, MiaPaca2, BxPc3, PL45, and Su.86.86) incubated with ACV-TP-T. The presence of ACV-TP-T and its metabolite inside the cells were analyzed by mass spectrometry. In vivo efficacy was evaluated in nude mice carrying PANC-1 or MiaPaca2 pancreatic xenograft tumors. RESULTS: The prodrug of ACV-TP-T was actively metabolized inside pancreatic cancer cells into the activated form of acyclovir; proliferation was reduced, apoptosis was increased, and the cell cycle was altered in pancreatic cancer incubated with ACV-TP-T, compared with controls. Administration of ACV-TP-T to mice reduced growth, increased apoptosis, and reduced proliferation and vascularization of pancreatic xenograft tumors. CONCLUSIONS:
|
Authors | Simone Polvani, Massimo Calamante, Valeria Foresta, Elisabetta Ceni, Alessandro Mordini, Alessandro Quattrone, Massimo D'Amico, Claudio Luchinat, Ivano Bertini, Andrea Galli |
Journal | Gastroenterology
(Gastroenterology)
Vol. 140
Issue 2
Pg. 709-720.e9
(Feb 2011)
ISSN: 1528-0012 [Electronic] United States |
PMID | 21044629
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Copyright | Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- Prodrugs
- Thymine Nucleotides
- acycloguanosyl 5'-thymidyltriphosphate
- Guanosine
- Telomerase
- Thymidine
|
Topics |
- Adenocarcinoma
(drug therapy)
- Animals
- Apoptosis
(drug effects)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Guanosine
(analogs & derivatives, analysis, therapeutic use)
- Humans
- Male
- Mice
- Mice, Nude
- Pancreatic Neoplasms
(drug therapy)
- Prodrugs
(therapeutic use)
- Telomerase
(metabolism)
- Thymidine
(metabolism)
- Thymine Nucleotides
(analysis, therapeutic use)
- Xenograft Model Antitumor Assays
|