Hepatitis B virus X protein (HBx) promotes hepatocellular carcinoma (HCC) invasion and metastasis by a poorly understood mechanism. This study investigated the role of NF-kappa B in HBx-mediated upregulation of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs). In a stably expressing HBx cell line, NF-kappa B level was examined by laser scanning confocal microscopy before and after treatment with pyrrolidine dithiocarbamate (PDTC; an NF-kappa B inhibitor). VEGF, MMP2, MMP9, and MMP14 mRNA and protein levels were quantitated by real-time PCR and Western blotting, respectively. HBx stimulated NF-kappa B signaling and increased VEGF, MMP2, MMP9, and MMP14 mRNA and protein levels. PDTC treatment blocked HBx-mediated stimulation of NF-kappa B signaling and decreased VEGF, MMP9, and MMP14 (but not MMP2) mRNA and protein levels. In vivo studies, PDTC reduced angiogenesis in subcutaneous xenograft of nude mice which injected HepG2-HBx cells. This suggests that NF-kappa B is involved in upregulating these genes and in the HBx-mediated invasion and metastasis of HCC.
基金:
National Natural Science Foundation of China [30430670]; Chinese Ministry of Public Health [353]; Hepatic Surgery Medical Clinical Research Centre of Hubei, China [2007]
第一作者单位:[1]Huazhong Univ Sci & Technol, Tongji Med Coll, Hepat Surg Ctr, Tongji Hosp, Wuhan, Hubei, Peoples R China
通讯作者:
推荐引用方式(GB/T 7714):
Liu Li-ping,Liang Hui-fang,Chen Xiao-ping,et al.The Role of NF-κB in Hepatitis B Virus X Protein-Mediated Upregulation of VEGF and MMPs[J].CANCER INVESTIGATION.2010,28(5):443-451.doi:10.3109/07357900903405959.
APA:
Liu, Li-ping,Liang, Hui-fang,Chen, Xiao-ping,Zhang, Wan-guang,Yang, Sheng-li...&Ren, Li.(2010).The Role of NF-κB in Hepatitis B Virus X Protein-Mediated Upregulation of VEGF and MMPs.CANCER INVESTIGATION,28,(5)
MLA:
Liu, Li-ping,et al."The Role of NF-κB in Hepatitis B Virus X Protein-Mediated Upregulation of VEGF and MMPs".CANCER INVESTIGATION 28..5(2010):443-451