Compound Astragalus and Salvia miltiorrhiza extract inhibits hepatocarcinogenesis via modulating TGF-β/TβR and Imp7/8
Compound Astragalus and Salvia miltiorrhiza extract inhibits hepatocarcinogenesis via modulating TGF-β/TβR and Imp7/8
复制标题
复方黄芪丹参提取物通过调节 TGF-β/TbetaR 和 Imp7/8 抑制肝癌发生。
DOI：
10.3892/etm.2018.6292
复制
发表时间：
2018-08-01
影响因子：
2.7
通讯作者：
Yang, Yan
中科院分区：
文献类型：
--
作者：
Wu, Chao;Kan, Hongwei;Yang, Yan
复方黄芪丹参提取物（CASE）是由黄芪和丹参中提取的黄芪甙、黄芪多糖和丹酚酸组成的中药配方。我们小组之前的研究表明，CASE 通过调节转化生长因子 β/Mothers 对抗去五肢麻痹 (TGF β/Smad) 信号传导，有效抑制二乙基亚硝胺 (DEN) 诱导的大鼠肝细胞癌 (HCC)。为了进一步阐明 CASE 的机制，本研究使用体内方法评估了 CASE 对 TGF-β(1)、TGF-β 丝氨酸/苏氨酸激酶受体 [TGF-β 受体 I 型 (T beta RI) 和 T beta RII] 和核转运蛋白 [Importin 7 (Imp7) 和 Imp8] 的影响，这些受体对于纤维性肝癌发生中的 TGF beta/Smad 信号传导至关重要。 （DEN 诱导的大鼠 HCC）和体外 [TGF-β(1) 刺激的大鼠肌成纤维细胞 (MFB) 和 HepG2 细胞] 纤维性肝癌发生模型。苏木精和伊红染色显示，CASE 可以抑制 HCC 的炎症反应和纤维化，并增加 HCC 细胞的分化。 DEN 治疗大鼠的 HCC 结节区域和邻近正常肝组织中阳性 TGF-β(1) 染色增加，而 TPRIE 染色仅在正常邻近肝组织中增加。 CASE 抑制了 TGF-β(1)、T β RI 和 T β RII 的升高表达。 CASE 治疗还降低了纤维性肝癌发生中谷胱甘肽 S-转移酶 P 1 和 Imp7/8 蛋白的表达。体外实验证实，CASE 能够降低 TGF-β(1) 刺激的 MFB 和 HepG2 细胞中 T β RI 和 T β RII 的表达。这些结果表明CASE的抗HCC作用可能是通过介导TGFβ/TβR和Imp7/8蛋白表达来实现的，这表明CASE在HCC治疗中具有多个靶点。
Compound Astragalus and Salvia miltiorrhiza extract (CASE) is a Chinese herbal formula consisting of astragalosides, astragalus polysaccharide and salvianolic acids extracted from Astragalus membranaceus and Salvia miltiorhiza. Previous studies by our group have demonstrated that CASE effectively suppresses diethylinitrosamine (DEN)-induced hepatocellular carcinoma (HCC) in rats via modulating transforming growth factor beta/Mothers against decapentaplegic (TGF beta/Smad) signaling. To further elucidate the mechanism of CASE, the effects of CASE on TGF-beta(1), the serine/threonine kinase receptors of TGF-beta [TGF-beta receptor type-I (T beta RI) and T beta RII] and karyopherins [Importin 7 (Imp7) and Imp8], which are crucial for TGF beta/Smad signaling in fibro-hepatocarcinogenesis, were assessed in the present study using in vivo (DEN-induced HCC in rats) and in vitro [TGF-beta(1)-stimulated rat myofibroblasts (MFBs) and HepG2 cells] models of fibro-hepatocarcinogenesis. Hematoxylin and eosin staining revealed that CASE may suppress inflammatory reactions and fibrosis in HCC as well as increasing the differentiation of HCC cells. Positive TGF-beta(1) staining was increased in HCC nodule areas and in adjacent normal liver tissues in DEN-treated rats, while TPRIE staining was increased only in normal adjacent liver tissues. The elevated expression of TGF-beta(1), T beta RI and T beta RII was suppressed by CASE. CASE treatment also reduced glut athione S-transferase P 1 and Imp7/8 protein expression in fibro-hepatocarcinogenesis. In vitro experiments confirmed that CASE was able to decrease the expression of T beta RI and T beta RII in TGF-beta(1)-stimulated MFBs and HepG2 cells. These results indicate that the anti-HCC effect of CASE may be achieved by mediating TGF beta/T beta R and Imp7/8 protein expression, suggesting that CASE has multiple targets in HCC treatment.