Lanzhou University of Technology, Lanzhou 730050, PR China.
Biochem Biophys Res Commun. 2011 Jul 15;410(4):803-8. doi: 10.1016/j.bbrc.2011.06.068. Epub 2011 Jun 15.
Members of the Spred gene family are negative regulators of the Ras/Raf-1/ERK pathway, which has been associated with several features of the tumor malignancy. However, the effect of Spred genes on hepatocellular carcinoma (HCC) remains uninvestigated. In the present work, we analyzed the in vitro and in vivo effects of Spred2 expression on the hepatic carcinoma cell line, SMMC-7721. In addition to attenuated ERK activation, which inhibited the proliferation and migration of unstimulated and HGF-stimulated SMMC-7721 cells. Adenovirus-mediated Spred2 overexpression induced the activation of caspase-3 and apoptosis, as well as reduced the expression level of Mcl-1. Most importantly, the knockdown of Spred2 markedly enhanced tumor growth in vivo. In conclusion, these results suggest that Spred2 could qualify as a potential therapeutic target in HCC.
Sprd 基因家族成员是 Ras/Raf-1/ERK 通路的负调节剂，该通路与肿瘤恶性的几个特征有关。然而，Sprd 基因对肝细胞癌 (HCC) 的影响尚未被研究。在本工作中，我们分析了 Sprd2 表达对肝癌细胞系 SMMC-7721 的体外和体内效应。除了减弱 ERK 激活外，Sprd2 还抑制了未刺激和 HGF 刺激的 SMMC-7721 细胞的增殖和迁移。腺病毒介导的 Sprd2 过表达诱导了 caspase-3 的激活和细胞凋亡，同时降低了 Mcl-1 的表达水平。最重要的是，Sprd2 的敲低显著增强了体内肿瘤的生长。总之，这些结果表明 Sprd2 可能是 HCC 的潜在治疗靶点。
