Open Access

Target therapy of TRIM-14 inhibits osteosarcoma aggressiveness through the nuclear factor-κB signaling pathway

  • Authors:
    • Yi‑Jiong Li
    • Guo‑Ping Zhang
    • Feng Zhao
    • Rui‑Qi Li
    • Shao‑Jun Liu
    • Zeng‑Ren Zhao
    • Xin Wang
  • View Affiliations

  • Published online on: December 27, 2017     https://doi.org/10.3892/etm.2017.5679
  • Pages: 2365-2373
  • Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Osteosarcoma is the most common cause of cancer-associated mortality and the prognosis is yet to be fully elucidated due to the paucity of effective therapeutic targets that significantly influence the quality of life and mean survival rates of patients with osteosarcoma. Studies have showed that tripartite motif‑containing (TRIM)‑14 is a member of the TRIM protein family that has a vital role in tumor progression and metastasis and promotes angiogenesis, invasion and apoptotic resistance of bone cancer. In this study, a chimeric antibody targeting TRIM‑14 (Chanti‑TRIM) was constructed and the molecular mechanism of target therapy for TRIM‑14 was investigated in osteosarcoma cells and xenograft mice. The growth, migration and invasion properties of U‑2OS cells were analyzed following incubation with 10‑160 mg/ml Chanti‑TRIM. Apoptosis of U‑2OS cells was detected after Chanti‑TRIM treatment. Matrix metalloproteinase (MMP)‑9‑mediated nuclear factor‑κB (NF‑κB) signal pathway was analyzed in U‑2OS cells treated with Chanti‑TRIM. The inhibitory efficacy of Chanti‑TRIM was studied in U‑2OS‑bearing xenograft mice. Our results demonstrated that neutralizing TRIM‑14 expression markedly inhibited the growth, migration and invasion of osteosarcoma cells, in vitro and in vivo. We found that TRIM‑14 depletion decreased cell viability and induced cells apoptosis in vitro. In addition, we identified Chanti‑TRIM inhibited growth and promoted apoptosis induced by cisplatin through MMP‑9‑mediated NF‑κB signal pathway. Furthermore, we observed that Chanti‑TRIM treatment inhibited osteosarcoma growth in vivo. Histological analysis indicated that apoptotic bodies were increased and NF‑κB nuclear translocation factors, including Ikkβ, p65 and IkBα, were decreased in tumors treated by Chanti‑TRIM. In conclusion, these results showed that Chanti‑TRIM markedly inhibited the progression of osteosarcoma, suggesting Chanti‑TRIM may be a potential anti‑cancer agent that functions via the activation of the NF‑κB pathway for osteosarcoma.
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March-2018
Volume 15 Issue 3

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Li YJ, Zhang GP, Zhao F, Li RQ, Liu SJ, Zhao ZR and Wang X: Target therapy of TRIM-14 inhibits osteosarcoma aggressiveness through the nuclear factor-κB signaling pathway. Exp Ther Med 15: 2365-2373, 2018
APA
Li, Y., Zhang, G., Zhao, F., Li, R., Liu, S., Zhao, Z., & Wang, X. (2018). Target therapy of TRIM-14 inhibits osteosarcoma aggressiveness through the nuclear factor-κB signaling pathway. Experimental and Therapeutic Medicine, 15, 2365-2373. https://doi.org/10.3892/etm.2017.5679
MLA
Li, Y., Zhang, G., Zhao, F., Li, R., Liu, S., Zhao, Z., Wang, X."Target therapy of TRIM-14 inhibits osteosarcoma aggressiveness through the nuclear factor-κB signaling pathway". Experimental and Therapeutic Medicine 15.3 (2018): 2365-2373.
Chicago
Li, Y., Zhang, G., Zhao, F., Li, R., Liu, S., Zhao, Z., Wang, X."Target therapy of TRIM-14 inhibits osteosarcoma aggressiveness through the nuclear factor-κB signaling pathway". Experimental and Therapeutic Medicine 15, no. 3 (2018): 2365-2373. https://doi.org/10.3892/etm.2017.5679