title: Silencing NOB1 enhances doxorubicin antitumor activity of the papillary thyroid carcinoma in vitro and in vivo.
abstract: Doxorubicin (DOX), a broad‑spectrum anthra-cyclin, is in wide clinical use for the treatment and prevention of thyroid cancer. However, the effectiveness of the treatment remains limited due to inherent tumor resistance to DOX. Results of a previous study demonstrated that downregulation of NIN1/RPN12 binding protein 1 homolog (NOB1) expression via adenovirus expression vector carrying NOB1 siRNA (Ad/sh-NOB1) induced cancer apoptosis and increased the radiosensitivity of papillary thyroid carcinoma (PTC) cells. However, whether knockout NOB1 can decrease DOX resistance remains unclear. Therefore, in the present study, the effect of Ad/sh-NOB1 infection, independently or in combination with DOX, was determined in a PTC cell line to identify more effective therapeutics against PTC cancer. Furthermore, tumor growth ability in nude mice was determined to identify the combination treatment effect in tumorigenesis in vivo. The results showed that Ad/sh-NOB1 combined with DOX treatment in PTC cells significantly suppressed proliferation, colony formation, migration and invasion, and induced cell apoptosis and arrest in the G0/G1 stage as compared to Ad/sh-NOB1 or DOX monotherapy. We also found that this combination suppressed the tumor growth of a nude mouse model as compared to Ad/sh-NOB1 or DOX monotherapy. In addition, Ad/sh-NOB1 combined with DOX treatment significantly increased activation of the p38 MAPK pathway, which may contribute to inhibition of PTC cell growth and decreased DOX resistance. Taken together, the experimental results indicate that Ad/sh-NOB1 combined with DOX treatment is a potential drug candidate for the treatment of papillary thyroid carcinoma.
authors.affiliation: Department of Thyroid Surgery, The First Bethune Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Thyroid Surgery, The First Bethune Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Bing-Fei
authors.initials: BF
authors.lastname: Dong
authors.affiliation: Department of Thyroid Surgery, The First Bethune Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Pei-Song
authors.initials: PS
authors.lastname: Wang
authors.affiliation: Department of Thyroid Surgery, The First Bethune Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Pei-You
authors.initials: PY
authors.lastname: Ren
authors.affiliation: Department of Thyroid Surgery, The First Bethune Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Xue
authors.affiliation: Department of Thyroid Surgery, The First Bethune Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Xiao-Νan
authors.initials: XΝ
authors.lastname: Zhang
authors.affiliation: Department of Thyroid Surgery, The First Bethune Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Han
authors.affiliation: Department of Thyroid Surgery, The First Bethune Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Guang
authors.initials: G
authors.lastname: Chen
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002277:Carcinoma / Q000188:drug therapy* / Q000235:genetics; D002291:Carcinoma, Papillary; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D004789:Enzyme Activation; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000235:genetics; D009368:Neoplasm Transplantation; D009687:Nuclear Proteins / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins / Q000235:genetics*; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000235:genetics; D014183:Transplantation, Heterologous; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D000903:Antibiotics, Antineoplastic; C506664:NOB1 protein, human; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D004317:Doxorubicin; D048051:p38 Mitogen-Activated Protein Kinases; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9