Effect of low-molecular-weight heparin combined with doxorubicin on hepatocellular cancer cell migration in vitro.
- Author:
Kehong YANG
1
;
Linyan MA
;
Xiu CHENG
;
Chao CHEN
;
Mengxiao ZHANG
;
Hao LIU
;
Zhiwen JIANG
Author Information
- Publication Type:Journal Article
- MeSH: Cell Movement; drug effects; Cell Survival; Down-Regulation; Doxorubicin; pharmacology; Glucuronidase; chemistry; Hep G2 Cells; Heparin, Low-Molecular-Weight; pharmacology; Humans; Liver Neoplasms; pathology; Matrix Metalloproteinase 2; metabolism; Matrix Metalloproteinase 9; metabolism; Neoplasm Invasiveness; RNA, Messenger; Real-Time Polymerase Chain Reaction
- From: Journal of Southern Medical University 2014;34(7):1048-1052
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the anti-cancer effect of low-molecular-weight heparin (LMWH) combined with doxorubicin and explore the mechanism.
METHODSHepatocellular 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.
RESULTSHepG2 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.
CONCLUSIONSLMWH 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.
