Nattokinase Crude Extract Inhibits Hepatocellular Carcinoma Growth in Mice
Nattokinase Crude Extract Inhibits Hepatocellular Carcinoma Growth in Mice
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纳豆激酶粗提物抑制小鼠肝细胞癌生长
DOI：
10.4014/jmb.1812.12058
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发表时间：
2019-08-01
影响因子：
2.8
通讯作者：
Gong, Aihua
中科院分区：
文献类型：
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作者：
Yan, Yongmin;Wang, Yanjing;Gong, Aihua
纳豆激酶（NK，E.C. 3.4.21.62）是一种由纳豆枯草芽孢杆菌产生的丝氨酸蛋白酶，有望用于治疗血栓性疾病。在这项研究中，我们评估了 NK 对肝细胞癌 (HCC) 发展的影响，肝细胞癌是一种导致全世界发病率和死亡率的主要肝脏恶性肿瘤。通过离心从发酵培养基中分离出 NK (NCE) 粗提物，并分成三个级分 (30K)。建立原位HCC小鼠模型并通过口服灌胃给予NCE。进行 H&E 染色以检查 HCC 肝脏的病理学。采用免疫组织化学和免疫荧光法评估肝脏中FOXM1、CD31、CD44和波形蛋白的表达。与 PBS 组相比，NCE 使 HCC 小鼠的存活率提高至 31%，并减少腹水。低强度超声成像显示，NCE 治疗小鼠的低回声肿块面积较低，肿瘤生长显着减少。 IHC 染色显示 NCE 处理抑制了 FOXM1 的表达。免疫荧光结果显示 NCE 组 CD31、CD44 和波形蛋白水平较低。总而言之，这些数据表明来自枯草芽孢杆菌纳豆的 NCE 可提高 HCC 小鼠的存活率并抑制肿瘤生长。
Nattokinase (NK, E.C. 3.4.21.62) is a serine protease produced by Bacillus subtilis natto that shows promise for the treatment of thrombotic disease. In this study, we assessed the effects of NK on the development of hepatocellular carcinoma (HCC), a principal malignancy of the liver that causes morbidity and mortality worldwide. Crude extracts of NK (NCE) were isolated from fermentation medium by centrifugation and separated into three fractions (30K). Orthotopic HCC mouse models were established and NCE was administered by oral gavage. H&E staining was performed to examine the pathology of HCC livers. Immunohistochemistry and immunofluorescence were used to evaluate FOXM1, CD31, CD44 and vimentin expression in the liver. Compared to PBS groups, NCE increased the survival rates of HCC-bearing mice to 31% and decreased ascites. Low-intensity ultrasound imaging showed that the hypoechoic mass area was lower in NCE-treated mice and that tumor growth significantly decreased. IHC staining showed that the expression of FOXM1 was inhibited by NCE treatment. Immunofluorescence results revealed lower levels of CD31, CD44 and vimentin in the NCE groups. Taken together, these data demonstrate that NCE from Bacillus subtilis natto improves survival and inhibits tumor growth in HCC mice.