Therapeutic targeting of oncogenic transforming growth factor-β1 signaling by antisense oligonucleotides in oral squamous cell carcinoma

• Published in: Oncology reports Vol. 28; no. 2; pp. 539 - 544
• Main Authors: KIM, SEONG-GON, SONG, JI-YOUNG
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.08.2012; Spandidos Publications UK Ltd
• Subjects: Animals; Antigens; antisense; Cancer therapies; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - therapy; Cell growth; Cell Growth Processes - genetics; Gene expression; Growth factors; Humans; Immunohistochemistry; Lymphatic system; Male; Matrix Metalloproteinase 2 - biosynthesis; Matrix Metalloproteinase 2 - genetics; matrix metalloproteinase-2; Metastasis; Mice; Mice, Nude; Oligonucleotides, Antisense - administration & dosage; Oligonucleotides, Antisense - genetics; Oral cancer; Proliferating Cell Nuclear Antigen - biosynthesis; Proliferating Cell Nuclear Antigen - genetics; Signal Transduction; Squamous cell carcinoma; Survival Analysis; Tongue Neoplasms - genetics; Tongue Neoplasms - metabolism; Tongue Neoplasms - pathology; Tongue Neoplasms - therapy; Transforming Growth Factor beta1 - genetics; Transforming Growth Factor beta1 - metabolism; transforming growth factor-β1; Tumors; Xenograft Model Antitumor Assays; United States > US
• ISSN: 1021-335X; 1791-2431
• DOI: 10.3892/or.2012.1811

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.