Akademik Veri Yönetim Sistemi
MEDICINA BALEAR, sa.3, 2024 (ESCI)
Objective: Autophagy is a catabolic process for degrading dysfunctional proteins and organelles and closely associated with cancer cell survival under therapeutic, metabolic stress, hypoxia, starvation and lack of growth factors, contributing to resistance to therapies. However, the role of autophagy in Glioblastoma (GBM) is not clearified. Methods and results: In the present study, we investigated the role of autophagy in highly aggressive and metastatic GBM cells and demonstrated that the knockdown of light chain 3 (LC3) with LC3-siRNAs which is considered as potential markers of autophagic activity, inhibited autophagy and significantly suppressed cell proliferation, colony formation, migration in GBM cells. Also, combination of Temozolamide (TMZ) and LC3-siRNA significantly inhibited autophagic activity, cell proliferation, colony formation, migration in GBM cells. Furthermore, knockdown of LC3 led to inhibition of multiple proto-oncogenic signaling pathways, including cyclin D1, integrin-beta 1/Src, and PARP1. Our findings suggest for the first time that LC3 are required for cell proliferation, survival, migration and may contribute to tumor growth and progression in by targeting cyclin D1, integrin-beta 1, Src, and PARP1 oncogenic signaling in GBM cells. Conclusion: Overall, these results suggesting, LC3-targeted combination treatments may be a potential therapeutic strategy for GBM and enhanced the efficacy of TMZ.