[Effect of low-molecular-weight heparin combined with doxorubicin on hepatocellular cancer cell migration in vitro].

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.

CONCLUSIONS:

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.

• Authors: Kehong Yang, Linyan Ma, Xiu Cheng, Chao Chen, Mengxiao Zhang, Hao Liu, Zhiwen Jiang
• Journal: Nan fang yi ke da xue xue bao = Journal of Southern Medical University (Nan Fang Yi Ke Da Xue Xue Bao) Vol. 34 Issue 7 Pg. 1048-52 (Jun 2014) ISSN: 1673-4254 [Print] China
• PMID: 25057082 (Publication Type: Journal Article)

Chemical References

• Heparin, Low-Molecular-Weight
• RNA, Messenger
• Doxorubicin
• heparanase
• Glucuronidase
• MMP2 protein, human
• Matrix Metalloproteinase 2
• MMP9 protein, human
• Matrix Metalloproteinase 9

Topics

• 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