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

• Published in: Indian journal of pathology & microbiology Vol. 56; no. 3; pp. 190 - 195
• Main Authors: Long, Xin Hua, Zhang, Zhi Hong, Liu, Zhi Li, Huang, Shan Hu, Luo, Qing Feng
• Format: Journal Article
• Language: English
• Published: India Medknow Publications and Media Pvt. Ltd 01-07-2013; Wolters Kluwer Medknow Publications
• Subjects: Adenosine Triphosphatases - antagonists & inhibitors; AKT/nuclear factor of kappa B; Blotting, Western; Cell Cycle Proteins - antagonists & inhibitors; Cell Line, Tumor; Cell Movement; Cellular proteins; Development and progression; Diagnosis; Gene Silencing; Humans; immunohistochemistry; metastasis; Neoplasm Metastasis - prevention & control; NF-kappa B - metabolism; Oncogene Protein v-akt - metabolism; Osteosarcoma; Osteosarcoma - prevention & control; Osteosarcoma - secondary; Physiological aspects; Signal Transduction; Transcription factors; Valosin Containing Protein; India
• ISSN: 0377-4929; 0974-5130
• DOI: 10.4103/0377-4929.120358

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.
Expression of VCP in 60 OS specimens was detected by immunohistochemistry (IHC) and the relationship with metastasis was analyzed. An artificial 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 protein 65 were measured by western blot to evaluate the effect of silencing VCP on AKT/nuclear factor of kappa B (NF-kB) signaling pathway.
The results showed that the expression level of VCP protein in cases with pulmonary metastases was significantly 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-kB.
Our findings suggested that inhibition of VCP could suppress OS cells invasion and migration through down-regulating AKT/NF-kB signaling pathway.