Shandong First Medical University, Shandong Provincial Hospital, Department of Orthopaedics, Jinan City, China.
J Appl Biomed. 2021 Dec;19(4):190-201. doi: 10.32725/jab.2021.021. Epub 2021 Sep 24.
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.
NF-κB 在多种人类癌症中被激活。然而，其在骨肉瘤（OS）中的作用尚不清楚。在这里，我们阐明了 NF-κB 在 OS 肿瘤细胞致癌表型中的作用。我们报道 NF-κB 的激活是人类 OS 的常见事件。使用抑制剂 Bay 11-7085 抑制 NF-κB 会抑制 143B 和 MG63 OS 细胞的增殖、存活、迁移和侵袭，但会增加细胞凋亡，表明 NF-κB 对 OS 的发生至关重要。值得注意的是，Bay 11-7085 不仅使 NF-κB 失活，而且通过诱导 PTEN 降低 AKT 的磷酸化，提示存在一种新的 NF-κB/PTEN/PI3K/AKT 轴。在体内，Bay 11-7085 通过靶向 NF-κB 和 AKT 抑制骨内肿瘤生长。有趣的是，Bay 11-7085 与 PI3K 抑制剂 LY294002 联合治疗引发了增强的抗肿瘤作用。我们的结果表明 NF-κB 增强了 OS 的生长和侵袭性。NF-κB 的药理抑制代表了治疗 OS 的一种有前途的疗法。
