مقالات پذیرفته شده در هشتمین کنگره بین المللی زیست پزشکی
Evaluation of the possible effects of AZD1152-HQPA on cellular and molecular aspects of apoptosis and cell migration in glioblastoma, focusing on miRNAs expression pattern
Evaluation of the possible effects of AZD1152-HQPA on cellular and molecular aspects of apoptosis and cell migration in glioblastoma, focusing on miRNAs expression pattern
Morteza Talebi Gharamaleki,1,*Ali Ghorbani,2seyyed mohammad kahani,5
1. Department of Medical Genetics and Molecular Biology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran 2. Iranian Biological resources center, Tehran, Iran 5. Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
Introduction: Glioblastoma (GBM) is a highly invasive and deadly central nervous system tumor, accounting for 14.9% of primary brain and CNS tumors. The incidence is higher in males and white individuals. Despite current treatments, the median survival rate post-diagnosis is only 18 months. Aurora kinase B (AURKB), essential for mitotic processes, is frequently overexpressed in cancers, including GBM. AZD1152, an AURKB inhibitor, disrupts these processes, presenting a potential therapeutic approach. This study investigates the effects of AZD1152-HQPA on GBM cells, focusing on miRNA expression, cell migration, and apoptosis.
Methods: U87MG GBM cells were cultured and treated with AZD1152-HQPA. Cytotoxic effects were assessed using MTT assay, Trypan Blue Exclusion Test, and Colony Formation Assay. Flow cytometry evaluated DNA content and apoptosis. Morphological changes were analyzed with DAPI staining. Cell migration was assessed via Scratch Assay. miRNA expression was analyzed using microarray data from GEO datasets GSE158284 and GSE25632, followed by qRT-PCR validation. Functional enrichment and miRNA-mRNA network analysis were conducted to understand the pathways involved.
Results: AZD1152-HQPA exhibited dose-dependent cytotoxicity, reducing U87MG cell viability and proliferation. Flow cytometry revealed increased polyploidy and apoptosis, with significant DNA content changes and multinucleated cells. AZD1152-HQPA inhibited cell migration. Microarray analysis identified 88 differentially expressed miRNAs, with significant changes in 79. Upregulated miRNAs included miR-196a and miR-200c, while downregulated miRNAs included miR-34a and miR-181c. Functional enrichment highlighted pathways like ECM receptor interaction, cell cycle, p53 signaling, and PI3K/Akt.
Conclusion: AZD1152-HQPA effectively inhibits GBM cell proliferation, induces apoptosis, and alters miRNA expression profiles. These miRNAs, involved in key oncogenic pathways, suggest that AZD1152-HQPA disrupts critical cellular processes in GBM. This study supports the potential of AZD1152-HQPA as a therapeutic agent for GBM, highlighting the importance of targeting AURKB and associated miRNAs to mitigate tumor growth and progression. Further investigation into the molecular mechanisms and clinical applications is warranted to enhance GBM treatment strategies.