The effect of temozolomide on apoptosis-related gene expression changes in glioblastoma cells

Abstract

BACKGROUND: Glioblastoma (GB) is the most common and biologically the most aggressive primary brain tumor of the central nervous system (CNS) in adults. Standard treatment for newly diagnosed GB consists of surgical resection, radiotherapy, and chemotherapy with temozolomide (TMZ). Despite numbers of studies, a resistance to chemotherapy is the major obstacle to successful GB treatment. OBJECTIVES: The aim of our study was to detect the sensitivity of glioblastoma T98G cells to TMZ treatment and subsequently to determine the expression changes of apoptosis-associated genes in glioblastoma cells. MATERIAL AND METHODS: The human glioblastoma cell line (T98G) was treated with specifi ed concentrations of TMZ during different time periods. Their viability was measured by colorimetric MTT assay and the activation of the apoptotic pathway was determined by measuring the caspase 3/7 activity. Commercial pre-designed microfl uidic array was used to quantify expression of human apoptosis-associated genes. RESULTS: The untreated control of T98G cell line against human brain total RNA standards reported signifi cant changes in several apoptotic genes expression levels. We identifi ed also a deregulation in gene expression levels between the TMZ treated and untreated T98G cells associated with apoptotic pathways. After 48 hours of exposure of T98G cells to TMZ, we observed a signifi cant deregulation of seven genes: BBC3, BCL2L1, RIPK1, CASP3, BIRC2, CARD6 and DAPK1. These results can contribute to the importance of apoptosis in glioblastoma cells metabolism and effect of TMZ treatment. CONCLUSIONS: Identifi cation of apoptotic gene panel in T98G cell line could help to improve understanding of brain tumor cells metabolism. Recognizing of the pro-apoptotic and anti-apoptotic genes expression changes could contribute to clarify the sensitivity to TMZ therapy and molecular base in healthy and tumor cells (Tab. 1, Fig. 2, Ref. 48).

The effect of Azo-dyes on glioblastoma cells in vitro

“…It has been reported that TMZ induced apoptosis in U87MG GB cell line at therapeutic dose, and decreased the expression levels of Vascular Endothelial Growth Factor (VEGF) and C-X-C chemokine receptor type 4 (CXCR4) ( Mirabdaly et al, 2020 ). Recently, another GB cell line T98G who underwent two days treatment with TMZ showed significant deregulation of 7 genes: BCL2L1, BBC3, BIRC2, RIPK1, CASP3, DAPK1 and CARD6 involved in apoptosis ( Vidomanova et al, 2022 ).…”