دورية أكاديمية
Bispecific antibody suppresses osteosarcoma aggressiveness through regulation of NF-κB signaling pathway
العنوان: | Bispecific antibody suppresses osteosarcoma aggressiveness through regulation of NF-κB signaling pathway |
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المؤلفون: | Gui-Hua Yu, Ai-Min Li, Xiang Li, Zhong Yang, Hao Peng |
المصدر: | Tumor Biology, Vol 39 (2017) |
بيانات النشر: | IOS Press, 2017. |
سنة النشر: | 2017 |
المجموعة: | LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
مصطلحات موضوعية: | Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
الوصف: | Osteosarcoma is one of the most lethal malignancies, and the prognosis remains dismal due to the paucity of effective therapeutic targets. Bmi-1 and TRIM-14 are associated with the initiation and progression of osteosarcoma, which could promote angiogenesis, invasion, and apoptotic resistance in bone cancer tissue. In this study, we constructed a bispecific antibody of BsAbBmi/TRIM targeting Bmi-1 and TRIM-14 and investigated the therapeutic value in bone carcinoma cells and xenograft mice. Our results showed that Bmi-1 and TRIM-14 expression levels were markedly upregulated correlated with nuclear factor-κB nuclear translocation in bone cancer cells and clinical carcinoma tissues. Results have demonstrated that overexpression of Bmi-1 and TRIM-14 promoted growth, proliferation, aggressiveness, and apoptosis resistance of osteosarcoma cells. BsAbBmi/TRIM administration significantly inhibited nuclear factor-κB expression derived by matrix metalloproteinase–9 promoter. BsAbBmi/TRIM administration inhibited growth of osteosarcoma cells and downregulated Bmi-1 and TRIM-14 expression levels. Data also demonstrated that migration and invasion of osteosarcoma cells were also inhibited by BsAbBmi/TRIM. In addition, results illustrated that BsAbBmi/TRIM inhibited tumor growth and tumorigenicity by blockaded sensor expression in nuclear factor-κB signal pathway. Furthermore, in vivo study showed that BsAbBmi/TRIM treatment markedly inhibited the tumorigenicity and growth of osteosarcoma cells compared to either AbBmi-1 or AbTRIM-14 treatment. Notably, survival of xenograft mice was prolonged by BsAbBmi/TRIM treatment compared to either AbBmi-1 or AbTRIM-14 treatment. In conclusion, these results provided new evidence that BsAbBmi/TRIM inhibited the progression of osteosarcoma, which suggest that BsAbBmi/TRIM may be a novel anti-cancer agent for osteosarcoma therapy. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 1423-0380 10104283 |
Relation: | https://doaj.org/toc/1423-0380 |
DOI: | 10.1177/1010428317705572 |
URL الوصول: | https://doaj.org/article/80fb160a4e554909a5f4f348c6dedb74 |
رقم الأكسشن: | edsdoj.80fb160a4e554909a5f4f348c6dedb74 |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 14230380 10104283 |
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DOI: | 10.1177/1010428317705572 |