DNAzymes to mouse beta1 integrin mRNA in vivo: targeting the tumor vasculature and retarding cancer growth.
Previously, we designed a DNAzyme (beta1DE) targeting the human beta1 integrin subunit, which efficiently digested the mRNA of the beta1 integrin subunit and downregulated beta1 integrin expression in endothelial cells. This DNAzyme blocked the adhesion of endothelial cells and abolished their ability to form microcapillary tubes in Matrigel. In our present study, we demonstrate that beta1DE effectively inhibited neovascularization in Matrigel plugs (BALB/c mice, n=20) and solid human carcinoma tumors developed in nude mice (BALB/cA nude (nu-/-)-B6.Cg-Foxn1(nu)) (n=30) using prostate carcinoma cells PC-3 (n=15) and colon adenocarcinoma cells CX1.1 (n=15). When injected intratumorally, it significantly reduced the tumor size and number of microvessels developed by both CX1.1 and PC-3 cells within the 3 weeks of experiment duration. Thus, DNAzymes targeting beta1 integrin genes can inhibit multiple key tumorigenic processes in vitro and in vivo and may serve as useful anti-cancer agents.
Niewiarowska
J
J
Department of Molecular and Medical Biophysics, Medical University of Lodz, Lodz 92-215, Poland.
Sacewicz
I
I
Wiktorska
M
M
Wysocki
T
T
Stasikowska
O
O
Wagrowska-Danilewicz
M
M
Cierniewski
C S
CS
D000818:Animals; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D021881:DNA, Catalytic / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
D021881:DNA, Catalytic; D019012:Integrin beta1; D012333:RNA, Messenger