title: Distinct inhibitory efficiency of siRNAs and DNAzymes to β1 integrin subunit in blocking tumor growth.
abstract: Receptors of the β1 integrin family are involved in many tumor-promoting activities. There are several approaches currently used to control integrin activity, and thus to potentially restrain tumor metastasis and angiogenesis. In this study, we compared inhibitory efficiencies of siRNA and DNAzymes against the β1 integrin subunit (DEβ1), in a mouse xenograft model. Both inhibitors were used under their most favorable conditions, in terms of concentrations, incubation time and lack of cytotoxic effects. Transfection of siRNAβ1 or DEβ1 remarkably inhibited the growth of both PC3 and HT29 colon cancer cells in vitro, and decreased their capability of initiating tumor formation in the mouse xenograft model. siRNAβ1 appeared to be slightly more efficient than DEβ1 when tested in vitro, however it was comparably less proficient in blocking the tumor growth in vivo. We conclude the DNAzyme, due to its greater resistance to degradation in extra- and intracellular compartments, to be a superior inhibitor of tumor growth in long lasting experiments in vivo when compared to siRNA, while the latter seems to be more efficient in blocking β1 expression during in vitro experiments using cell cultures.
authors.affiliation: Department of Molecular and Medical Biophysics, Medical University of Lodz, Łódź, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Wiktorska
authors.forename: Izabela
authors.initials: I
authors.lastname: Sacewicz-Hofman
authors.forename: Olga
authors.initials: O
authors.lastname: Stasikowska-Kanicka
authors.forename: Marian
authors.initials: M
authors.lastname: Danilewicz
authors.forename: Jolanta
authors.initials: J
authors.lastname: Niewiarowska
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015153:Blotting, Western; D002448:Cell Adhesion; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy; D021881:DNA, Catalytic / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D019073:HT29 Cells; D006801:Humans; D007150:Immunohistochemistry; D019012:Integrin beta1 / Q000235:genetics*; D051379:Mice; D034741:RNA, Small Interfering / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D021881:DNA, Catalytic; D019012:Integrin beta1; D034741:RNA, Small Interfering