title: Inhibitory effects of STAT3 decoy oligodeoxynucleotides on human epithelial ovarian cancer cell growth in vivo.
abstract: The signal transducer and activator of transcription 3 (STAT3) regulates target gene expression by binding to a consensus DNA sequence within the promoter of the target genes. The constitutive activation of STAT3 has been shown to contribute to tumorigenesis in ovarian cancer and it has been reported to be a key factor for drug resistance in ovarian cancer. STAT3-specific decoy oligodeoxynucleotides (ODNs) (STAT3 decoy ODNs) that contain a consensus DNA sequence inhibit the transcriptional activity of STAT3, leading to cancer cell death. However, their mechanisms of action are unclear and little information is available as to the effects and the toxicity of STAT3 decoy ODNs in vivo. In this study, we established subcutaneous xenografts of SKOV3 human ovarian cancer cells in nude mice, evaluated the antitumor effects of STAT3 decoy ODNs on xenografted nude mice, and investigated the mechanisms behind the antitumor effects of STAT3 decoy ODNs targeting the STAT3 signaling pathway in vivo. The results revealed that the STAT3 decoy ODN inhibited ovarian cancer cell growth and promoted ovarian cancer cell apoptosis in vivo. Western blot analysis indicated that the STAT3 decoy ODN downregulated the protein expression levels of matrix metalloproteinase (MMP)-2, MMP-9 and Bcl-2, and upregulated the protein expression levels of caspase-3 in vivo. H&E staining was used to detect the side-effects of the STAT3 decoy ODN in the vital organs of the nude mice. We found that there were no significant abnormalities in the vital organs of the nude mice apart from slight inflammation and necrosis in parts of the hepatic lobule. The data from the present study suggest that decoy ODNs targeting STAT3 may be an effective therapeutic approach for the treatment of ovarian cancer in vivo.
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Zhang
authors.forename: Peishu
authors.initials: P
authors.lastname: Liu
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Hongluan
authors.initials: H
authors.lastname: Mao
authors.forename: Liang
authors.initials: L
authors.lastname: Shen
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Ma
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D000077216:Carcinoma, Ovarian Epithelial; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology* / Q000633:toxicity; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D009838:Oligodeoxyribonucleotides; D019253:Proto-Oncogene Proteins c-bcl-2; D050796:STAT3 Transcription Factor; D053148:Caspase 3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9