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 HPAexpressions.