Dextran Sulfate Sodium Prevents Tumor Growth By Inhibiting Matrix Metalloproteinases Expression

Matrix metalloproteinases (MMPs) are zinc-dependent proteolytic enzymes and well known for their capability of degrading all kinds of extracellular matrix proteins to offer help in tumor migration. Recent research developments have markedly advanced our understanding of MMPs as important modulators in tumor microenvironment in which MMPs can not only regulate signaling pathways that control cell growth, but also regulate apoptosis and angiogenesis activities. These aspects of MMPs function are reorienting our approaches to cancer therapy. Cationic materials with nucleic acid drug delivery ability are widely used in clinical studies. Recent studies have shown their interactions with immune systems and tumor growth.However, the relationship between tumor and anionic polymers, such as Dextran sulfate sodium (Dss), is rarely studied. Our studies tried to find out how Dss may affect macrophage and cancer. After incubation with Dss, the supernatant from cultured macrophage cells was assayed for IL-6、TNF-α、IL-4、IL-10 and IL-12. By using qRT-PCR and Western Blot methods, we tried to know if Dss could make significant changes of MMPs expression. To further evaluate the potential anti-tumor effect of Dss, we built the tumor-bearing mice model. And by using Western Blot、 H&E staining and fluorescence staining methods, we examined the levels of MMPs and CD31 in Dss-treated mice. The results show us that, in vitro, Dss declined the levels of MMP-9 by 72.72% and MMP-2 by 73.68% in macrophages. And in the murine allograft tumor model, we investigated that anionic polymers may inhibit levels of MMPs to evoke therapeutic anti-tumor activities.