Compound Astragalus and Salvia miltiorrhiza extracts suppress hepatocarcinogenesis by modulating transforming growth factor-β/Smad signaling
Compound Astragalus and Salvia miltiorrhiza extracts suppress hepatocarcinogenesis by modulating transforming growth factor-β/Smad signaling
复制标题
复方黄芪和丹参提取物通过调节转化生长因子-β/Smad 信号传导抑制肝癌发生
DOI：
10.1111/jgh.12490
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发表时间：
2014-06-01
影响因子：
4.1
通讯作者：
Yang, Yan
中科院分区：
文献类型：
--
作者：
Hu, Xiangpeng;Rui, Wenjuan;Yang, Yan
背景与目的研究表明黄芪和丹参的提取物复方黄芪丹参提取物（Compound Astragalus and Salvia miltiorrhiza extract，CASE）对二乙基亚硝胺（diethylinnitrosamine，DEN）诱导的大鼠肝细胞癌（hepatocellular carcinoma，HCC）有明显的抑制作用，体外实验进一步证实CASE抗HepG 2细胞侵袭作用与转化生长因子-（transforming growth factor-，TGF-）有关。我们假设，CASE的肝癌的抑制是由TGF-/Smad信号调制，我们进行了这项在体内研究，以测试这一hypothes.MethodsRats分为正常对照组，DEN组，和三个CASE（60，120，和240 mg/kg）治疗组。结果DEN组大鼠肝癌结节区及癌旁相对正常肝组织中pSmad 2L和pSmad 3L阳性染色均明显增强，P <0.01，P而pSmad 2C和pSmad 3C仅在癌旁相对正常的肝组织中表达增强。CASE以剂量依赖性方式抑制pSmad 2C、pSmad 2L、pSmad 3L、Smad 4和纤溶酶原激活物抑制剂1蛋白的表达。CASE治疗也显着减少了pSmad 2L和pSmad 3L的核内量，并上调pSmad 3C阳性细胞和蛋白表达的升高，在一个剂量依赖marticle.ConclusionThe结果表明，CASE显着抑制肝癌的进展，通过介导TGF-/Smad信号，特别是通过调节Smad 3磷酸化的C-末端和连接区。
Background and AimPrevious studies showed Compound Astragalus and Salvia miltiorrhiza extract (CASE), extract from Astragalus membranaceus and Salvia miltiorhiza, significantly suppresses hepatocellular carcinoma (HCC) in rats induced by diethylinitrosamine (DEN), and in vitro experiments further demonstrated that CASE's anti-HepG2 cell invasion is associated with transforming growth factor- (TGF-). We hypothesized that CASE's suppression of HCC is modulated by TGF-/Smad signaling, and we conducted this in vivo study to test this hypothesis.MethodsRats were divided into the normal control, the DEN group, and three CASE (60, 120, and 240mg/kg) treatment groups. The expression of phosphorylation(p) Smad both at C-terminal and linker region, plasminogen activator inhibitor 1, and Smad4 and Smad7 of liver tissues were measured and compared across the five groups.ResultsThe positive staining of pSmad2L and pSmad3L increased both in hepatoma nodule areas and adjacent relatively normal liver tissues in rats treated with DEN, while the positive staining of pSmad2C and pSmad3C increased only in relatively normal liver tissues adjacent to hepatoma tissues. The elevated expression of pSmad2C, pSmad2L, pSmad3L, Smad4, and plasminogen activator inhibitor 1 proteins were suppressed by CASE in a dose-dependent manner. CASE treatment also significantly reduced the intranuclear amounts of pSmad2L and pSmad3L, and upregulated the elevation of pSmad3C positive cells and protein expression in a dose-dependent manner.ConclusionThe results suggest that CASE significantly suppresses HCC progression by mediating TGF-/Smad signaling, especially by modulating Smad3 phosphorylation both at the C-terminal and linker region.