Bispecific antibody suppresses osteosarcoma aggressiveness through regulation of NF-κB signaling pathway
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 bon...
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2017-06-01
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| Series: | Tumor Biology |
| Online Access: | https://doi.org/10.1177/1010428317705572 |
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| _version_ | 1849251150129266688 |
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| author | Gui-Hua Yu Ai-Min Li Xiang Li Zhong Yang Hao Peng |
| author_facet | Gui-Hua Yu Ai-Min Li Xiang Li Zhong Yang Hao Peng |
| author_sort | Gui-Hua Yu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-80fb160a4e554909a5f4f348c6dedb74 |
| institution | Kabale University |
| issn | 1423-0380 |
| language | English |
| publishDate | 2017-06-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Tumor Biology |
| spelling | doaj-art-80fb160a4e554909a5f4f348c6dedb742025-08-20T03:57:03ZengSAGE PublishingTumor Biology1423-03802017-06-013910.1177/1010428317705572Bispecific antibody suppresses osteosarcoma aggressiveness through regulation of NF-κB signaling pathwayGui-Hua Yu0Ai-Min Li1Xiang Li2Zhong Yang3Hao Peng4Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei, ChinaBasic Medical College, Wuhan University, Wuhan, Hubei, ChinaBasic Medical College, Wuhan University, Wuhan, Hubei, ChinaBasic Medical College, Wuhan University, Wuhan, Hubei, ChinaDepartment of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei, ChinaOsteosarcoma 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.https://doi.org/10.1177/1010428317705572 |
| spellingShingle | Gui-Hua Yu Ai-Min Li Xiang Li Zhong Yang Hao Peng Bispecific antibody suppresses osteosarcoma aggressiveness through regulation of NF-κB signaling pathway Tumor Biology |
| title | Bispecific antibody suppresses osteosarcoma aggressiveness through regulation of NF-κB signaling pathway |
| title_full | Bispecific antibody suppresses osteosarcoma aggressiveness through regulation of NF-κB signaling pathway |
| title_fullStr | Bispecific antibody suppresses osteosarcoma aggressiveness through regulation of NF-κB signaling pathway |
| title_full_unstemmed | Bispecific antibody suppresses osteosarcoma aggressiveness through regulation of NF-κB signaling pathway |
| title_short | Bispecific antibody suppresses osteosarcoma aggressiveness through regulation of NF-κB signaling pathway |
| title_sort | bispecific antibody suppresses osteosarcoma aggressiveness through regulation of nf κb signaling pathway |
| url | https://doi.org/10.1177/1010428317705572 |
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