Al-Gayyar Mohammed M H, Abbas Ahmed, Hamdan Ahmed M
Biol Chem. 2016 Mar;397(3):257-67. doi: 10.1515/hsz-2015-0265.
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 μg/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 nfκb and TNF-α 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.
硫酸酯酶2（SULF2）是一种细胞外酶，可催化从硫酸乙酰肝素（HS）中去除6-O-硫酸基团。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一种SULF2抑制剂在体内和体外对肝细胞癌的化学保护和肝脏保护作用。使用硫代乙酰胺（200mg/kg）诱导大鼠发生HCC。治疗组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，脂联素均完全阻断了HCC诱导的SULF2升高。脂联素的抗肿瘤活性通过以下结果得到证实：存活率提高80%，每只带瘤肝脏的平均结节数减少73%，血清甲胎蛋白减少46%。此外，脂联素改善了HCC诱导的肿瘤侵袭标志物MMP9、多配体蛋白聚糖-1和FGF-2的表达。此外，脂联素减弱了HCC诱导的nfκb和TNF-α水平升高。此外，用脂联素处理HepG2细胞系显示出HepG2细胞活力的剂量依赖性降低和细胞毒性的升高。此外，脂联素在HepG2细胞中也产生了相同的剂量依赖性结果。脂联素通过阻断SULF2对HCC实现了肝脏保护和化学保护作用。
