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J Microbiol Biotechnol. 2019 Jul 29. doi: 10.4014/jmb.1812.12058. [Epub ahead of print]

Natokinase crude extract inhibits hepatocellular carcinoma growth in mice.

Author information

1
Key Laboratory of Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, 212013, Jiangsu, P. R. China.

Abstract

Nattokinase (NK, EC 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 malignant tumor that causes morbidity and mortality worldwide. Crudes extracts of NK (NCE) were isolated from fermentation medium by centrifugation and separated into three fractions (<10 K, 100~30 K and >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 the Bacillus subtilis natto improves survival and inhibits tumor growth in HCC mice.

KEYWORDS:

cancer; hepatocellular carcinoma; nattokinase; tumor growth

PMID:
31370114
DOI:
10.4014/jmb.1812.12058
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