Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 515, Issue 1, Pages 57-63Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2019.04.063
Keywords
Cell migration and invasion; Matrine; Metalloproteinase-9; Liver cancer
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Funding
- earmarked fund for Tianjin Medical Research System [20170101257TC]
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Matrine is a natural compound derived from Radix Sophora flavescens which is a commonly used Chinese herb. Herein, we report that matrine may inhibit lung metastasis in liver cancer in mice. Invasion chamber assay, scratch-wound assay and orthotopic liver tumor implantation mice were introduced to investigate the potential pharmacological effects of matrine on human hepatocellular carcinoma (HCC). Our results showed that matrine at non-toxic dose could significantly suppress PLC/PRF/5 and MHCC97L cells migration and invasion. Furthermore, matrine treatment (5 mg/kg/day) significantly decreased lung metastasis in orthotopic HCC mouse models. Quantitative polymerase chain reaction, gelatin zymography and immunoblotting assay indicated that matrine could inhibit the activity of matrix metalloproteinase-9 without down-regulating its protein expression in HCC. The docking approach, site-directed mutagenesis, and surface plasmon resonance were applied to identify residues involved in matrine binding in matrix metalloproteinase-9. The biophysical and cell-based assays showed that Pro415, Arg424 residue might contribute to the binding affinity of matrine on matrix metalloproteinase-9 activity. In conclusion, matrine might be a promising anti-cancer agent for inhibiting HCC metastasis. (C) 2019 Elsevier Inc. All rights reserved.
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