Journal
CARBOHYDRATE POLYMERS
Volume 174, Issue -, Pages 282-290Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.carbpol.2017.06.072
Keywords
Carboxymethyl chitosan; Norcantharidin; Anti-hepatoma; Liver-protection; Orthotopic transplantation
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Funding
- China Postdoctoral Science Foundation [861705020012]
- Key Research & Development Program of Shandong Province [2016YYSP018]
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In this study, norcantharidin (NCTD), a small-molecule anticancer drug derived from Chinese traditional medicine blister beetle (Mylabris), was conjugated covalently onto carboxymethyl chitosan (CMCS). Then the hepatocellular carcinoma therapeutic properties and liver-protective effects were investigated through orthotopic transplantation tumor model. Results showed that the obtained CMCS-NCTD demonstrated remarkable anti-growth efficacy against hepatocellular 22 in mice. Significant improvement of the liver injury caused by cancer cells was observed in tumor-bearing mice administrated with CMCS-NCTD. Moreover, CMCS-NCTD remarkably increased the serum levels of TNF-alpha, IFN-beta, TIMP-1 and E-cadherin in mice treated for 12 days. Administration of CMCS-NCTD significantly reduced the elevated serum ALT, AST, VEGF and MMP-9 levels of tumor-bearing mice. In addition, activities of SOD and GSH-Px in serum or homogenate of the CMCS-NCTD treated mice were significantly high when compared with model control group. Our data suggested that CMCS-NCTD was a promising candidate as an anti-hepatoma and liver-protection compound. (C) 2017 Elsevier Ltd. All rights reserved.
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