title: Differences in antitumor effects of various statins on human pancreatic cancer.
abstract: Statins are widely used for the treatment of hypercholesterolemia. However, their inhibitory action on HMG-CoA reductase also results in the depletion of intermediate biosynthetic products, which importantly contribute to cell proliferation. The aim of the present study was to compare the effects of the individual commercially available statins on experimental pancreatic cancer. The in vitro effects of individual statins (pravastatin, atorvastatin, simvastatin, lovastatin, cerivastatin, rosuvastatin and fluvastatin) on the viability of human pancreatic cancer were evaluated in CAPAN-2, BxPc-3 and MiaPaCa-2 cell lines. The in vivo experiments were performed on nude mice xenotransplanted with CAPAN-2 cells. The mice received oral treatments either with a placebo, or with the statins mentioned earlier in a daily dose corresponding to a hypocholesterolemic dose in humans. The effect of these statins on the intracellular Ras protein, trafficking in MiaPaCa-2 transfected cells, was also investigated. Substantial differences in the tumor-suppressive effects of all statins were detected in both in vitro and in vivo experiments. While simvastatin exerted the highest tumor-suppressive effects in vitro, rosuvastatin (p = 0.002), cerivastatin (p = 0.002) and fluvastatin (p = 0.009) were the most potent compounds in an animal model. All statins (except pravastatin) inhibited intracellular Ras protein translocation. In summary, substantial tumor-suppressive effects of various statins on the progression of experimental pancreatic adenocarcinoma were demonstrated, with marked differences among individual statins. These results support greatly the potential of statins for the chemoadjuvant treatment of pancreatic cancer.
authors.affiliation: Department of Biochemistry and Microbiology and Center for Applied Genomics, Institute of Chemical Technology, Prague, Czech Republic.
authors.forename: Helena
authors.initials: H
authors.lastname: Gbelcová
authors.forename: Martin
authors.initials: M
authors.lastname: Lenícek
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Zelenka
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Knejzlík
authors.forename: Gabriela
authors.initials: G
authors.lastname: Dvoráková
authors.forename: Marie
authors.initials: M
authors.lastname: Zadinová
authors.forename: Pavla
authors.initials: P
authors.lastname: Poucková
authors.forename: Michal
authors.initials: M
authors.lastname: Kudla
authors.forename: Peter
authors.initials: P
authors.lastname: Balaz
authors.forename: Tomás
authors.initials: T
authors.lastname: Ruml
authors.forename: Libor
authors.initials: L
authors.lastname: Vítek
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D017931:DNA Primers; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000473:pathology*; D016133:Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors