اثر ایزوسورباید بر فعالیت ماتریکس متالوپروتئینازها در رده‌های سلولی فیبرو سارکومایی 164-Wehi و لوسمیک 1-THPدر شرایط آزمایشگاهی

Background and purpose: Matrix metalloproteinases (MMPs) are a group of enzymes degredating the extracellular matrix. MMPs have an important role in inflammation, tumor growth, metastasis and angiogenesis. Among the MMPs, MMP1 and MMP2 have special implication in angiogenesis. Isosorbide, as a nitric oxide donor, has been widely used in treatment of many cardiovascular diseases. Besides the inhibitory effect of isosorbide on angiogenesis, tumor growth and metastasis has been revealed in vivo. Regarding the important role of MMPs in tumor growth, metastasis and angiogenesis and also the suppressive effect of isosorbide on angiogenesis, tumor growth and metastasis, In this study, the isosorbide effect on MMP-2 and MMP-9 activity of leukemic and fibrosarcoma cells has been evaluated. Materials and methods: The leukemic THP-1 and fibrosarcoma Wehi-164 cells were cultured in complete RPMI medium. Then the cells in the presence of phorbol myristate acetate (PMA) (25 ng/ml), incubated with different concentrations of isosorbide (0.0004, 0.004, 0.04, and 0.4 mM) for 24 hours. Thereafter, the isosorbide effect on MMP-2 and MMP-9 activity of the cells was evaluated by gelatin zymography assay. Statistical comparisons between the groups were done by analysis of variance (ANOVA). Results: The MMPs activity of PMA-stimulated leukemic THP-1 and fibrosarcoma Wehi-164 cells treated with different concentrations of isosorbide did not show any statistical significant difference with untreated control cells. Conclusion: The results of this study demonstrated that isosorbide had no statistical significant effect on MMPs activity of leukemic THP-1 and fibrosarcoma Wehi-164 cells. These findings proposed that anti- angiogenic effect of isosorbide, which was declared by other investigations, may possibly be owing to non-MMP activity mediated mechanisms.