The Repression of Matrix Metalloproteinases and Cytokine Secretion in Glioblastoma by Targeting K+ Channel

Basic and Clinical Neuroscience

article

Farshid Saadat¹  Zohreh Zareighane²  Farnaz Safavifar³  Seyedeh Zohreh Jalali¹  Azar Berahmeh²  Mohammad Reza Khorramizadeh³ 

[1] Department of Immunology, School of Medicine, Guilan University of Medical Sciences;Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences;Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences

关键词: Glioblastoma;    Interleukin-6;    4-Aminopyridine;    Matrix metalloproteinases;    Potassium channels;    Voltage-gated;   

DOI  :  10.32598/bcn.2021.1693.1

来源: Iran University of Medical Sciences

【 摘 要 】

Introduction: 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.  Methods: 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.  Results: 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. Conclusion: 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.

【 授权许可】

Unknown