Effect of low-molecular-weight heparin combined with doxorubicin on hepatocellular cancer cell migration in vitro
10.3969/j.issn.1673-4254.2014.07.27
- VernacularTitle:低相对分子质量肝素联合多柔比星对肝癌细胞迁移能力的影响
- Author:
Kehong YANG
1
;
Linyan MA
;
Xiu CHENG
;
Chao CHEN
;
Mengxiao ZHANG
;
Hao LIU
;
Zhiwen JIANG
Author Information
1. 蚌埠医学院药学系/安徽省生化药物工程技术研究中心
- Keywords:
hepatocellular cancer;
low-molecular-weight heparin;
doxorubicin;
migration;
matrix metalloproteinase-9;
matrix metalloproteinase-2;
heparanase
- From:
Journal of Southern Medical University
2014;(7):1048-1052
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the anti- cancer effect of low- molecular- weight heparin (LMWH) combined with doxorubicin and explore the mechanism. Methods Hepatocellular cancer HepG2 cells exposed to LMWH, doxorubicin, or both were evaluated for cell viability with MTT assay and for changes in their migration ability using wound healing assay and Transwell migration assay. The changes in cellular expressions of matrix metalloproteinase-9 (MMP-9) and MMP-2 mRNA and proteins were analyzed with quantitative real-time PCR (qRT-PCR) and Western blotting, and ELISA was used to determine heparanase (HPA) concentration in the cell culture medium. Results HepG2 cells exhibited suppressed proliferation in response to LMWH and doxorubicin treatments. The combined treatment caused a significantly higher inhibition rate of cell migration than LMWH and doxorubicin alone. LMWH enhanced doxorubicin-induced down-regulation of MMP-9, MMP-2 and HPA in the cells. Conclusion LMWH can enhance the inhibitory effect of doxorubicin on the migration of HepG2 cells, the mechanism of which may involve the down-regulation of MMP-9, MMP-2 and HPA expressions.
