Inhibiting valosin-containing protein suppresses osteosarcoma cell metastasis via AKT/nuclear factor of kappa B signaling pathway in vitro.

ABSTRACT

Background and Aim: The strategies of targeting valosin-containing protein (VCP) may have therapeutic potential for treating cancer metastasis. In this study, we aim to investigate the correlation of VCP protein expression in osteosarcoma (OS) tissues with pulmonary metastasis and its possible molecular mechanism. Materials and Methods: Expression of VCP in 60 OS specimens was detected by immunohistochemistry (IHC) and the relationship with metastasis was analyzed. An artifi cial micro ribonucleic acid, targeting VCP, was performed to silence the expression of VCP in U2-OS cells. Cell mobility was detected by wound healing and Transwell assays. Western blot and real-time polymerase chain reaction were performed to investigate the expression of VCP in U2-OS cells. Furthermore, the protein of pAKT (phosphorylated serine/threonine protein kinase) and nuclear factor of kappa B protein65 were measured by western blot to evaluate the effect of silencing VCP on AKT/nuclear factor of kappa B (NF-B) signaling pathway. Results: The results showed that the expression level of VCP protein in cases with pulmonary metastases was signifi cantly higher than that in those without metastasis (P = 0.004). The invasion and migration of U2-OS cells were suppressed by silencing VCP. Furthermore, silencing VCP could down-regulate the phosphorylation of AKT and nuclear transfer of NF-B. Conclusions: Our fi ndings suggested that inhibition of VCP could suppress OS cells invasion and migration through down-regulating AKT/NF-B signaling pathway.