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Bmi?1?targeting suppresses osteosarcoma aggressiveness through the NF??B signaling pathway.

ABSTRACT: Bone cancer is one of the most lethal malignancies and the specific causes of tumor initiation are not well understood. B?cell?specific Moloney murine leukemia virus integration site 1 protein (Bmi?1) has been reported to be associated with the initiation and progression of osteosarcoma, and as a prognostic indicator in the clinic. In the current study, a full?length antibody targeting Bmi?1 (AbBmi?1) was produced and the preclinical value of Bmi?1?targeted therapy was evaluated in bone carcinoma cells and tumor xenograft mice. The results indicated that the Bmi?1 expression level was markedly upregulated in bone cancer cell lines, and inhibition of Bmi?1 by AbBmi?1 reduced the invasiveness and migration of osteosarcoma cells. Overexpression of Bmi?1 promoted proliferation and angiogenesis, and increased apoptosis resistance induced by cisplatin via the nuclear factor??B (NF??B) signal pathway. In addition, AbBmi?1 treatment inhibited the tumorigenicity of osteosarcoma cells in vivo. Furthermore, AbBmi?1 blocked NF??B signaling and reduced MMP?9 expression. Furthermore, Bmi?1 promoted osteosarcoma tumor growth, whereas AbBmi?1 significantly inhibited osteosarcoma tumor growth in vitro and in vivo. Notably, AbBmi?1 decreased the percentages of Ki67?positive cells and terminal deoxynucleotidyl transferase dUTP nick end labeling?positive cells in tumors compared with Bmi?1?treated and PBS controls. Notably, MMP?9 and NF??B expression were downregulated by treatment with AbBmi?1 in MG?63 osteosarcoma cells. In conclusion, the data provides evidence that AbBmi?1 inhibited the progression of osteosarcoma, suggesting that AbBmi?1 may be a novel anti?cancer agent through the inhibition of Bmi?1 via activating the NF??B pathway in osteosarcoma.

SUBMITTER: Liu J

PROVIDER: S-EPMC5779877 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Bmi‑1‑targeting suppresses osteosarcoma aggressiveness through the NF‑κB signaling pathway.

Liu Jiaguo J Luo Bin B Zhao Meng M

Molecular medicine reports 20170928 6

Bone cancer is one of the most lethal malignancies and the specific causes of tumor initiation are not well understood. B‑cell‑specific Moloney murine leukemia virus integration site 1 protein (Bmi‑1) has been reported to be associated with the initiation and progression of osteosarcoma, and as a prognostic indicator in the clinic. In the current study, a full‑length antibody targeting Bmi‑1 (AbBmi‑1) was produced and the preclinical value of Bmi‑1‑targeted therapy was evaluated in bone carcinom ...[more]

PMID: 28983587

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Bmi?1?targeting suppresses osteosarcoma aggressiveness through the NF??B signaling pathway.

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Bmi‑1‑targeting suppresses osteosarcoma aggressiveness through the NF‑κB signaling pathway.

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