en Cellular and molecular Neuroscience Cellular and molecular Neuroscience Original Original <div style="text-align: justify;"><strong>Introduction: </strong>Glioblastoma is an aggressive human brain malignancy with poorly understood pathogenesis. Voltage-gated potassium (Kv) channels and Matrix Metalloproteinases (MMPs) are highly expressed in malignant tumors and involved in the progression and metastasis of glioblastoma. This study aimed to determine whether a voltage-dependent potassium channel blocker could modulate astrocytes as a cell involved in the immunopathogenesis of glioblastoma.&nbsp;<br> <strong>Methods: </strong>The cytotoxic effect of 4-Aminopyridine (4-AP) at different doses in the cell model of glioblastoma was measured by MTT assay. The ELISA technique and gelatin zymography were used to assess cytokine levels and MMP-9 after 4-AP treatment.&nbsp;<br> <strong>Results: </strong>Cytotoxicity analysis data indicated that cell viability reduced by increasing 4-AP level and cell growth decreased gradually by removing 4-AP from the cell medium. 4-AP inhibits the secretion of IL-6 and IL-1 (P<0.05). MMP9 activity significantly inhibits with increased 4-AP dose, compared to non-treated cells.<br> <strong>Conclusion: </strong>The reduction of cell viability, IL-6 secretion, and MMP-9 activity in an in vitro model of glioblastoma might be assumed 4-AP as an agent for chemoprevention of cancer.</div> Glioblastoma, Interleukin-6, 4-Aminopyridine, Matrix metalloproteinases, Potassium channels, Voltage-gated 737 744 http://bcn.iums.ac.ir/browse.php?a_code=A-10-1693-1&slc_lang=en&sid=1 Farshid Saadat fsaadat@alumnus.tums.ac.ir 13700319475328460039285 13700319475328460039285 No Department of Immunology, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran. Zohreh Zareighane zzareighane@gmail.com 13700319475328460039286 13700319475328460039286 No Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. Farnaz Safavifar fsafavifar@yahoo.com 13700319475328460039287 13700319475328460039287 No Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. Seyedeh Zohreh Jalali z_jalali@gums.ac.ir 13700319475328460039288 13700319475328460039288 No Department of Immunology, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran. Azar Berahmeh aberahmeh@yahoo.com 13700319475328460039289 13700319475328460039289 No Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. Mohammad Reza Khorramizadeh khoramza@tums.ac.ir 13700319475328460039290 13700319475328460039290 Yes Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.