Antimetastatic effects of liposomal gemcitabine and empty liposomes in an orthotopic mouse model of pancreatic cancer

• Published in: Pancreas Vol. 38; no. 3; p. 330
• Main Authors: Graeser, Ralph, Bornmann, Christian, Esser, Norbert, Ziroli, Vittorio, Jantscheff, Peter, Unger, Clemens, Hopt, Ulrich T, Schaechtele, Christoph, von Dobschuetz, Ernst, Massing, Ulrich
• Format: Journal Article
• Language: English
• Published: United States 01.04.2009
• Subjects: Animals; Antimetabolites, Antineoplastic - pharmacology; Cell Line, Tumor; Deoxycytidine - analogs & derivatives; Deoxycytidine - pharmacology; Disease Models, Animal; Drug Resistance, Neoplasm; Female; Liposomes - pharmacology; Luciferases - genetics; Mice; Mice, Nude; Neoplasm Transplantation; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - pathology; Peritoneal Neoplasms - secondary; Transduction, Genetic
• ISSN: 1536-4828
• DOI: 10.1097/MPA.0b013e31819436e6

Test the efficacy of liposomal gemcitabine (GemLip) on primary tumor and metastases using the pancreatic tumor cell line AsPC1 implanted orthotopically into nude mice. The efficacy of gemcitabine and GemLip cells was tested on luciferase-transduced AsPC1 cells in vitro as well as implanted orthotopically into the pancreata of nude mice. In vitro, the IC50s for GemLip and gemcitabine were 20 nM and 140 nM, respectively. However, when applied against established tumors, GemLip (8 mg/kg) blocked tumor growth for 5 consecutive weeks according to bioluminescence measurements in vivo. Gemcitabine (240 mg/kg) had no effect on luciferase-monitored tumor growth. When analyzed at the time of necropsy, GemLip strongly reduced tumor size (-64% +/- [SD] 27%; ***P < 0.0001), whereas gemcitabine only weakly (-36% +/- 37%) affected tumor size. Empty liposomes had no effect on the tumor size. GemLip and empty liposomes both significantly interfered with the metastatic spread to the liver, as measured using luciferase assays (GemLip, *P = 0.01; empty liposomes, *P = 0.036). In addition, they showed effects against spleen, as well as peritoneal metastases. GemLip presents an effective new formulation of gemcitabine, combining the targeting and protective features of the liposomes with their antimetastatic effects to target pancreatic cancer.