title: Anticancer activity of NOB1-targeted shRNA combination with TRAIL in epithelial ovarian cancer cells.
abstract: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) based strategy is a promising targeted therapeutic approach for the treatment of ovarian cancer. However, the effectiveness of the treatment remains limited due to the inherent or acquired resistance of tumor cells to TRAIL. Our previously study demonstrated that downregulation of NOB1 (NIN1/RPN12 binding protein 1 homolog) expression by a lentiviral short hairpin RNA (shRNA) delivery system (Lv/sh-NOB1) suppressed ovarian cancer growth. Here, Lv/sh-NOB1 and TRAIL were combined and tested the effects of this combination on ovarian cancer cells to identify more effective therapeutics against ovarian cancer by several in vitro experiments. Tumor growth ability in SKVO3 xenograft nude mice was also determined to define this combination treatment effect in tumorigenesis in vivo. In vitro assay showed that Lv/sh-NOB1 in combination with TRAIL treatment in ovarian cancer cell synergistically suppressed the proliferation and colony formation, as well as induced cell apoptosis and increased the activity of caspase-3, -8 and -9. In vivo assay showed that Lv/sh-NOB1 combination with TRAIL synergistically suppressed tumor growth of nude mice model. Importantly, we found that downregulation of NOB1 could upregulate DR5 expression and active MAPK pathway, which might contribute to increase sensitivity TRAIL to ovarian cancer cells. These findings suggested that Lv/sh-NOB1 combination with TRAIL treatment may be a potential treatment approach for ovarian cancer.
authors.affiliation: Department of Obstetrics and Gynecology, The Second Hospital, Jilin University #218 Ziqiagn Street, Nanguan District, Changchun 130041, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Obstetrics and Gynecology, The Second Hospital, Jilin University #218 Ziqiagn Street, Nanguan District, Changchun 130041, China.
authors.forename: Tianmin
authors.initials: T
authors.lastname: Xu
authors.affiliation: Department of Obstetrics and Gynecology, The Second Hospital, Jilin University #218 Ziqiagn Street, Nanguan District, Changchun 130041, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Teng
authors.affiliation: Department of Obstetrics and Gynecology, The Second Hospital, Jilin University #218 Ziqiagn Street, Nanguan District, Changchun 130041, China.
authors.forename: Manhua
authors.initials: M
authors.lastname: Cui
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D000077216:Carcinoma, Ovarian Epithelial; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C506664:NOB1 protein, human; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9
keywords: NOB1; Ovarian cancer; epithelial ovarian cancer