Open Access

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

  • Authors:
    • Jiaguo Liu
    • Bin Luo
    • Meng Zhao
  • View Affiliations

  • Published online on: September 28, 2017     https://doi.org/10.3892/mmr.2017.7660
  • Pages:7949-7958
  • Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

0

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‑κB (NF‑κB) signal pathway. In addition, AbBmi‑1 treatment inhibited the tumorigenicity of osteosarcoma cells in vivo. Furthermore, AbBmi‑1 blocked NF‑κB 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‑κB 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‑κB pathway in osteosarcoma.

Related Articles

Journal Cover

December 2017
Volume 16 Issue 6

Print ISSN: 1791-2997
Online ISSN:1791-3004

2016 Impact Factor: 1.692
Ranked #19/128 Medicine Research and Experimental
(total number of cites)

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Liu, J., Luo, B., & Zhao, M. (2017). Bmi‑1‑targeting suppresses osteosarcoma aggressiveness through the NF‑κB signaling pathway. Molecular Medicine Reports, 16, 7949-7958. https://doi.org/10.3892/mmr.2017.7660
MLA
Liu, J., Luo, B., Zhao, M."Bmi‑1‑targeting suppresses osteosarcoma aggressiveness through the NF‑κB signaling pathway". Molecular Medicine Reports 16.6 (2017): 7949-7958.
Chicago
Liu, J., Luo, B., Zhao, M."Bmi‑1‑targeting suppresses osteosarcoma aggressiveness through the NF‑κB signaling pathway". Molecular Medicine Reports 16, no. 6 (2017): 7949-7958. https://doi.org/10.3892/mmr.2017.7660