Chemopreventive and hepatoprotective roles of adiponectin (SULF2 inhibitor) in hepatocelluar carcinoma
Chemopreventive and hepatoprotective roles of adiponectin (SULF2 inhibitor) in hepatocelluar carcinoma
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DOI：
10.1515/hsz-2015-0265
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发表时间：
2016-03-01
影响因子：
3.7
通讯作者：
Hamdan, Ahmed M.
中科院分区：
文献类型：
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作者：
Al-Gayyar, Mohammed M. H.;Abbas, Ahmed;Hamdan, Ahmed M.
硫酸酯酶 2 (SULF2) 是一种胞外酶，可催化硫酸乙酰肝素 (HS) 中 6-O-硫酸基的去除。由于 SULF2 活性升高与肝细胞癌 (HCC) 相关，因此本研究旨在评估脂联素作为 SULF2 抑制剂在体内和体外对肝细胞癌的化学保护和肝保护作用。使用硫代乙酰胺（200 mg/kg）在大鼠中诱导 HCC。治疗大鼠每周接受一次脂联素（5μg/kg）。此外，使用人肝细胞癌（HepG2）细胞系作为体外模型。在体内和体外模型中，脂联素完全阻断 HCC 诱导的 SULF2 升高。脂联素的抗肿瘤活性被证实可以使存活率提高 80%，每个带有结节的肝脏的平均结节数量减少 73%，血清 AFP 减少 46%。此外，脂联素改善了 HCC 诱导的肿瘤侵袭标志物 MMP9、syndecan-1 和 FGF-2 的表达。此外，脂联素可减弱 HCC 诱导的 nf kappa b 和 TNF-α 水平升高。此外，用脂联素处理 HepG2 细胞系显示出剂量依赖性的 HepG2 细胞活力降低和细胞毒性升高。此外，脂联素在 HepG2 细胞中以剂量依赖性方式产生相同的结果。脂联素通过阻断 SULF2 实现对 HCC 的保肝和化学保护作用。
Sulfatase 2 (SULF2) is an extracellular enzyme that catalyzes the removal of 6-O-sulfate groups from the heparan sulfate (HS). As elevated SULF2 activity has been correlated with hepatocellular carcinoma (HCC), this study was conducted to evaluate the chemoprotective and the hepatoprotective roles of adiponectin, as a SULF2 inhibitor, against hepatocellular carcinoma both in vivo and in vitro. HCC was induced in rats using thioacetamide (200 mg/kg). Treated rats received adiponectin (5 mu g/kg) once a week. Moreover, human hepatocellular carcinoma (HepG2) cell line was used as an in-vitro model. In both-in-vivo and in-vitro models, adiponectin completely blocked HCC-induced SULF2 elevation. The antitumor activity of adiponectin was confirmed by 80% increased the survival rate, 73% reduction in the average number of nodules per nodule-bearing liver and 46% reduction in serum AFP. In addition, adiponectin ameliorated -HCC-induced expression of tumor invasion markers, MMP9, syndecan-1 and FGF-2. Moreover, adiponectin attenuated HCC-induced elevation of nf kappa b and TNF-alpha levels. Moreover, treatment of HepG2 cell line with adiponectin showed dose-dependent reduction of HepG2 cell viability and elevation of cellular cytotoxicity. Besides, Adiponectin yielded the same results in HepG2 cells in a dose-dependent manner. Adiponectin achieved both hepatoprotective and chemoprotective effects against HCC through blocking of SULF2.