Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Cancer Invest. 2010 Jun;28(5):443-51. doi: 10.3109/07357900903405959.
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.
乙型肝炎病毒 X 蛋白 (HBx) 通过一种尚未完全了解的机制促进肝细胞癌 (HCC) 的侵袭和转移。本研究探讨了 NF-κB 在 HBx 介导的血管内皮生长因子 (VEGF) 和基质金属蛋白酶 (MMPs) 上调中的作用。在稳定表达 HBx 的细胞系中，通过激光共聚焦显微镜在使用吡咯烷二硫代氨基甲酸盐 (PDTC; NF-κB 抑制剂) 处理前后检查 NF-κB 水平。通过实时 PCR 和 Western blot 分别定量 VEGF、MMP2、MMP9 和 MMP14 mRNA 和蛋白水平。HBx 刺激 NF-κB 信号通路并增加 VEGF、MMP2、MMP9 和 MMP14 mRNA 和蛋白水平。PDTC 处理阻断 HBx 介导的 NF-κB 信号通路的刺激，并降低 VEGF、MMP9 和 MMP14(但不降低 MMP2)mRNA 和蛋白水平。在体内研究中，PDTC 减少了裸鼠皮下注射 HepG2-HBx 细胞的皮下异种移植物中的血管生成。这表明 NF-κB 参与上调这些基因，并参与 HBx 介导的 HCC 侵袭和转移。
