J Appl Biomed 19:190-201, 2021 | DOI: 10.32725/jab.2021.021

The NF-κB pathway is critically implicated in the oncogenic phenotype of human osteosarcoma cells

Bingyi Tan, Zenong Yuan, Qingyu Zhang, Xu Xiqiang, Jun Dong^*

Shandong First Medical University, Shandong Provincial Hospital, Department of Orthopaedics, Jinan City, China

NF-κB is activated in a variety of human cancers. However, its role in osteosarcoma (OS) remains unknown. Here, we have elucidated the implication of NF-κB in the oncogenic phenotype of OS tumor cells. We reported that activation of NF-κB was a common event in the human OS. Inhibition of NF-κB using inhibitor Bay 11-7085 repressed proliferation, survival, migration, and invasion but increased apoptosis in 143B and MG63 OS cells, indicating that NF-κB is critically implicated in the oncogenesis of OS. Notably, Bay 11-7085 not only inactivated NF-κB but also reduced the phosphorylation of AKT via its induction of PTEN, suggesting the existence of a novel NF-κB/PTEN/PI3K/AKT axis. In vivo, Bay 11-7085 suppressed tumor growth in the bone by targeting NF-κB and AKT. Interestingly, combined treatment with Bay 11-7085 and the PI3K inhibitor, LY294002, triggered an augmented antitumor effect. Our results demonstrate that NF-κB potentiates the growth and aggressiveness of OS. Pharmacological inhibition of NF-κB represents a promising therapy for the treatment of OS.

Keywords: AKT; NF-κB; Osteosarcoma; Treatment

Grants and funding:

This study was supported by the Shandong Provincial Medical Technology & Development Program, China (2019WS459) to J.D.

Conflicts of interest:

There is no competing interest related to the manuscript.

Received: February 15, 2021; Revised: September 9, 2021; Accepted: September 23, 2021; Prepublished online: September 24, 2021; Published: December 6, 2021  Show citation