The role of NF-kappaB in Hepatitis b virus X protein-mediated upregulation of VEGF and MMPs.
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.
Liu
Li-ping
LP
Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Liang
Hui-fang
HF
Chen
Xiao-ping
XP
Zhang
Wan-guang
WG
Yang
Sheng-li
SL
Xu
Tao
T
Ren
Li
L
D000818:Animals; D056945:Hep G2 Cells; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology*; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D011759:Pyrrolidines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013859:Thiocarbamates / Q000494:pharmacology; D015534:Trans-Activators / Q000378:metabolism*; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins
D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; D015534:Trans-Activators; D042442:Vascular Endothelial Growth Factors; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; C020972:pyrrolidine dithiocarbamic acid; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D053511:Matrix Metalloproteinase 14