Repression of Matrix Metalloproteinases and Cytokine Secretion in Glioblastoma by Targeting K+ Channel: An in Vitro Study

Abstract

Introduction: Glioblastoma is an aggressive malignancy of human brain 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. The purpose of this study was to determine whether a voltage-dependent potassium channel blocker could modulate astrocytes as a cell which involved in immunopathogenesis of glioblastoma. Methods: The cytotoxic effect of 4-aminopyridine (4-AP) at different doses in cell model of glioblastoma was measured by MTT assay. ELISA technique and gelatin zymography were used to assess cytokines levels and MMP-9 after 4-AP treatment, respectively. Results: Cytotoxicity analysis showed that cell viability reduced by increasing 4-AP level and cell growth reduced gradually by removing 4-AP from cell medium. 4-AP inhibits secretion of IL-6 and IL-1 (p<0.05). MMP9 activity significantly inhibits with increased 4-AP dose as compared to non-treated cells. Conclusion: 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.