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首页> 外文期刊>Integrative cancer therapies >Inhibition of Hepatocellular Carcinoma by Total Alkaloids of Rubus alceifolius Poir Involves Suppression of Hedgehog Signaling
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Inhibition of Hepatocellular Carcinoma by Total Alkaloids of Rubus alceifolius Poir Involves Suppression of Hedgehog Signaling

机译：茜草总生物碱对肝癌的抑制作用涉及刺猬信号的抑制

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Objective. We evaluated the effects of total alkaloids of Rubus alceifolius Poir (TARAP) on the migration and invasion of hepatocellular carcinoma (HCC) and furthermore investigated the possible molecular mechanisms mediating its anticancer activity. Methods. We implanted nude mice with human HCC HepG2 cells and fed them with vehicle (physiological saline) or 3 g/kg/day dose of TARAP 5 days per week for 21 days. We determined the in vitro effect of TARAP on the migration and invasion of HepG2 cells by transwell assay. We evaluated SHH signaling components' (SHH, PTCH, SMO, and Gli1) expression levels by reverse transcriptase-polymerase chain reaction and immunohistochemistry. Activity of the matrix metalloproteinases (MMPs) in supernatants was analyzed by zymography. The expression of the MMPs and their specific tissue inhibitor (tissue inhibitor of matrix metalloproteinases, TIMP-1, 2) in HCC tissues was detected by immunohistochemistry. Results. We discovered that TARAP inhibited hepatocellular migration and invasion in a dose-dependent manner in vitro. In addition, TARAP decreased the expression of SHH, PTCH, SMO, and Gli1 in HCC mouse tumors at both transcriptional and translational levels. Moreover, TARAP inhibited the activity of MMP2 and MMP9. We found that TARAP reduced the expression of MMP2 and MMP9, as well as the tissue inhibitor of MMPs. Conclusion. Our study showed that TARAP inhibits HCC migration and invasion likely through suppression of the hedgehog pathway. This may, in part, explain its anticancer properties. These results suggest that total alkaloids in Rubus alceifolius may have potential as a novel antimetastasis drug in the treatment of HCC.
机译：目的。我们评估了悬钩子总生物碱（TARAP）对肝细胞癌（HCC）迁移和侵袭的影响，并进一步研究了介导其抗癌活性的可能分子机制。方法。我们向裸鼠植入了人类HCC HepG2细胞，并每周5天给它们喂食媒介物（生理盐水）或3 g / kg /天剂量的TARAP，共21天。我们通过transwell测定法测定了TARAP对HepG2细胞迁移和侵袭的体外作用。我们通过逆转录聚合酶链反应和免疫组化评估了SHH信号成分（SHH，PTCH，SMO和Gli1）的表达水平。上清液中基质金属蛋白酶（MMP）的活性通过酶谱分析。通过免疫组织化学检测MMPs及其特异性组织抑制剂（基质金属蛋白酶组织抑制剂，TIMP-1，2）在肝癌组织中的表达。结果。我们发现TARAP在体外以剂量依赖性方式抑制肝细胞迁移和侵袭。此外，TARAP可以在转录和翻译水平上降低HCC小鼠肿瘤中SHH，PTCH，SMO和Gli1的表达。此外，TARAP抑制MMP2和MMP9的活性。我们发现TARAP降低了MMP2和MMP9的表达以及MMPs的组织抑制剂。结论。我们的研究表明，TARAP可能通过抑制刺猬通路来抑制HCC迁移和侵袭。这可以部分解释其抗癌特性。这些结果表明，悬钩子中的总生物碱可能具有作为新型抗转移药物治疗HCC的潜力。

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