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

Pancreas
R GraeserU Massing

Abstract

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 pr...Continue Reading

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Citations

Feb 21, 2009·Cancer Chemotherapy and Pharmacology·Khalid Abu AjajFelix Kratz
Sep 29, 2009·Clinical & Experimental Metastasis·Peter JantscheffUlrich Massing
Apr 25, 2012·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Thomas PoeschingerWerner Scheuer
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