索拉非尼通过抑制 ERK/NF-κB 通路抑制 TPA 诱导的肝癌细胞 MMP-9 和 VEGF 表达。
Sorafenib inhibits TPA-induced MMP-9 and VEGF expression via suppression of ERK/NF-κB pathway in hepatocellular carcinoma cells.
机构信息
Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, and Department of Radiation Oncology and Hospice Care Center, Mackay Memorial Hospital, No. 155, Sec. 2, Li-Nong St., Bei-tou, Taipei 112, Taiwan, ROC.
出版信息
In Vivo. 2012 Jul-Aug;26(4):671-81.
Invasion by hepatocellular carcinoma (HCC) has been reported to occur via the up-regulation of nuclear factor-kappaB (NF-κB). Sorafenib can improve the overall survival in patients with HCC, however, the association of its inhibitory mechanisms with the inactivation of NF-κB remains unclear. Here, Huh7 cell line transfected with NF-κB-luc2 vector was used to study the effects of sorafenib on NF-κB activity, on expressions of matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF), which were induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). TPA increased the NF-κB activity and the expressions of MMP-9 and VEGF significantly, but its effects were suppressed by sorafenib in a dose-dependent manner. Similar results were found with PD98059, an inhibitor of extracellular signal-regulated kinase (ERK). Furthermore, transfection of Huh7 cell with an inhibitor of kappaB-α mutant vector, led to reduced TPA-induced MMP-9 and VEGF mRNA expressions. Sorafenib inhibits TPA-induced MMP-9 and VEGF expressions via the suppression of ERK/NF-κB pathway in HCC cells.
已有研究报道，肝癌（HCC）的侵袭是通过核因子-κB（NF-κB）的上调而发生的。索拉非尼可改善 HCC 患者的总生存期，但它的抑制机制与 NF-κB 的失活之间的关联尚不清楚。在这里，我们使用转染 NF-κB-luc2 载体的 Huh7 细胞系来研究索拉非尼对 NF-κB 活性、基质金属蛋白酶-9（MMP-9）和血管内皮生长因子（VEGF）表达的影响，这些都是由 12-O-十四烷酰佛波醇-13-乙酸酯（TPA）诱导的。TPA 显著增加了 NF-κB 活性和 MMP-9 和 VEGF 的表达，但索拉非尼可呈剂量依赖性抑制其作用。ERK 抑制剂 PD98059 也得到了类似的结果。此外，转染 Huh7 细胞的 κB-α 突变体载体，导致 TPA 诱导的 MMP-9 和 VEGF mRNA 表达减少。索拉非尼通过抑制 HCC 细胞中的 ERK/NF-κB 通路抑制 TPA 诱导的 MMP-9 和 VEGF 表达。
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