Author:
Neykhonji Marzieh,Nazem Shima,Ghaedi Hamid,Mirzaei Alireza,Tavakoli-Yaraki Masoumeh,Shahsavari Zahra
Abstract
Background: Among the primary bone tumors, osteosarcoma accounts for a malignant tumor with a high rate of progression and poor prognosis. Despite the achievement of combined therapy regimens in improving patients’ overall survival, patients with osteosarcoma confront the chemoresistance obstacle. Objectives: This study aimed at determining the expression pattern of autophagy and necroptosis pathways mediators in osteosarcoma tumors. Methods: The expression level of autophagy main mediators such as autophagy-associated protein 5 (ATG5), Beclin 1 (BECN1), and microtubule-associated protein 1A/1B-light chain 3 (LC3), necroptosis biomarkers such as receptor-interacting protein kinases (RIPK1 and RIPK3), and mixed lineage kinase domain-like (MLKL) were evaluated in 80 bone tissues including 60 bone tumors (40 malignant tumors and 20 benign tumors) and 20 margin tissues, using real-time PCR. The correlations of gene expression levels with the patient’s clinical and pathological features were considered. Results: Based on our data, ATG5, BECN1 and LC3 expression were down-regulated in osteosarcoma tumors compared to margin tissues. Also, malignant osteosarcoma tumors showed a significant decrease in the expression level of RIPK1 and MLKL as necroptosis regulators, which revealed a correlation with tumor malignancy. In addition, the higher expression levels of BECN1, LC3, RIPK1, and MLKL were observed in tumor tissues of patients under the chemotherapy regimen, indicating the relevance of autophagy and necroptosis pathways with the patient’s response to therapy. Conclusions: Reduction in the expression level of autophagy and necroptosis mediators in high-grade osteosarcoma tumors indicates the possible impact of these pathways on the rate of proliferation and growth of osteosarcoma tumor cells and can emphasize the importance of cell death alternative pathways for treatment when apoptosis machinery is mutated and cause chemoresistance.
Subject
Pharmacology (medical),Cancer Research,Radiology, Nuclear Medicine and imaging,Oncology,Surgery