title: Therapeutic targeting of oncogenic transforming growth factor-β1 signaling             by antisense oligonucleotides in oral squamous cell carcinoma.
abstract: The transforming growth factor-β1 (TGF-β1) signaling pathway is important             in human oral squamous cell carcinoma (OSCC). Accordingly, the aims of this study             were to evaluate the effect of antisense TGF-β1 oligonucleotides (ODNs) on OSCC             in cell culture and in a xenograft model, as well as to evaluate any effects ODNs             have on proliferating cell nuclear antigen (PCNA) and matrix metalloproteinase-2             (MMP-2) expression in the xenograft model. We performed real-time cell electronic             sensing (RT-CES) to determine the effect of antisense TGF-β1 ODNs on SCC-9 cell             growth. To examine the in vivo effect of antisense TGF-β1 ODN therapy, SCC-9 cells             were grafted into nude mice. Antisense ODNs were injected into the mass daily.             Tumor size, body weight and duration of survival were assessed daily. Specimens             from the main mass were used for immunohistochemical staining to analyze PCNA             and MMP-2 expression. In vitro treatment with antisense TGF-β1 ODNs decreased             TGF-β1 expression and growth of SCC-9 cells. In the xenograft model, the antisense             TGF-β1 ODN group exhibited a significantly decreased tumor growth rate compared             to the control, which received Dulbecco's modified Eagle's medium (DMEM) (P=0.022).             However, mean survival time and body weights were not significantly different             between the groups (P>0.05). Immunohistochemistry showed that tumors from animals             that received antisense TGF-β1 ODNs had significantly lower expression levels             of PCNA and MMP-2 compared to tumors from animals in the DMEM group (P<0.05).             In conclusion, antisense TGF-β1 ODN therapy significantly inhibits tumor growth             compared to controls, however, there are no significant differences between groups             with respect to changes in body weight.
authors.affiliation: Department of Oral and Maxillofacial Surgery, College of Dentistry, Gangneung-Wonju National University, Gangneung 210-702, Republic of Korea. epker@chol.com
authors.forename: Seong-Gon
authors.initials: SG
authors.lastname: Kim
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Song
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D048708:Cell Growth Processes / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage* / Q000235:genetics; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction; D016019:Survival Analysis; D014062:Tongue Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D053773:Transforming Growth Factor beta1 / Q000235:genetics* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D016376:Oligonucleotides, Antisense; D018809:Proliferating Cell Nuclear Antigen; D053773:Transforming Growth Factor beta1; D020778:Matrix Metalloproteinase 2