Knockdown Of Aurora-B Inhibits Osteosarcoma Cell Invasion And Migration Via Modulating PI3K/akt/NF-κB Signaling Pathway

Objective:To investigate the inhibitory effect of Aurora-B on invasion and migration of OS cells and the activity of PI3K/Akt/NF-κB signaling pathway in vitro.Methods:The recombinant lentivirus targeting Aurora-B gene was constructed. There are named with LV-shAURKB(LV-shAURKB-1、LV-shAURKB-2、LV-shAURKB-3)and Negative control LV-NC. Human U2-OS OS cells and HOS cells were treated with LV-shAURKB or LV-NC. The mRNA level of Aurora-B was measured by qRT-PCR. The expression of Aurora-B and p-Akt(Ser473) proteins was detected by immunohistochemistry in OS tissues from 24 patients with pulmonary metastatic disease, and the relationship between Aurora-B and p-Akt(Ser473) was investigated.Transwell assay and Migration assay was used to evaluate the invasion and migration ability of U2-OS cells and HOS cells which treated with LV-shAURKB or LV-NC,respectively. Western blot analysis was also performed to detect the protein experession of Aurora-B、p-Akt(Ser473)、Akt、p-PI3K(Tyr199)、PI3K 、NF-κB(p65)and β-actin.Results:○1 The qRT-PCR and western blot results showed that the levels of Aurora-B mRNA and protein were significantly blocked in OS cells which treated with LV-shAURKB than LV-NC.○2 The Immunohistochemical staining results in OS tissues from 24 patients with pulmonary metastatic disease showed a significant positive correlation between phosphorylated Akt(p-Akt) and the expression of FASN(R=0.726, P=0.02).○3 The transwell and wound healing results showed that Inhibiting Aurora-B blocked OS cells invasion and migration.○4 The western blot results showed that PI3 K, p-PI3K(Tyr199), and p-Akt(Ser473), NF-κB(p65) protein expressions in OS cells were blocked by inhibiting Aurora-B. But the Akt protein expression was no significant difference.Conclusion:Our results indicated that knockdown of Aurora-B suppresses OS cells migratory and invasive ability partial via modulating the “PI3K/Akt/NF-κB” signaling pathway in vitro. The Aurora-B blocker may be a new therapeutic strategy in OS management...