Antagonistic Effects of Temozolomide and Sialic Acid on Bax Gene Expression in Glioma Cells: Implications for Chemoresistance
Antagonistic Effects of Temozolomide and Sialic Acid on Bax Gene Expression in Glioma Cells: Implications for Chemoresistance
Farideh Rezaei,1Mohammad Shafiei,2,*Hamid Galehdari,3Alireza Malayeri,4Seyed Mehdi Kalantar,5
1. Department of Biology, Faculty of Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran 2. Department of Biology, Faculty of Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran 3. Department of Biology, Faculty of Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran 4. Medical Plant Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran 5. Research & Clinical Center for Infertility, Shahid Sadoughi Medical Sciences University, Yazd, Iran
Introduction: Glioma, a primary tumor of the central nervous system, is resistant to various treatments, including chemotherapy. Temozolomide (TMZ) is a first-line chemotherapy drug used for glioma treatment; however, the tumor microenvironment, including factors such as sialic acid, can influence drug resistance and treatment outcomes. This study aims to investigate the effects of TMZ, sialic acid, and their combined treatment on Bax gene expression in glioma cells, with a focus on apoptosis regulation. Bax, a pro-apoptotic member of the Bcl-2 family, plays a critical role in promoting cell death.
Methods: Glioma 1321N1 cells were cultured under standard laboratory conditions and treated with temozolomide (100 µM) and sialic acid (300 µM), both individually and in combination, over a 72-hour period. Gene expression analysis of Bax was performed using real-time PCR to assess changes in apoptosis regulation under different treatments.
Results: The results revealed that treatment with temozolomide increased Bax gene expression, indicating enhanced apoptosis in glioma cells. In contrast, treatment with sialic acid alone led to a sharp decrease in Bax expression, suggesting an inhibitory effect on apoptosis. Interestingly, the combined treatment of temozolomide and sialic acid resulted in a pronounced reduction in Bax expression, indicating that sialic acid might counteract the pro-apoptotic effects of temozolomide. This suppression of Bax expression in the presence of sialic acid suggests that it may play a role in reducing the effectiveness of temozolomide, potentially contributing to the survival of cancer cells and resistance to chemotherapy.
Conclusion: This study highlights the potential of sialic acid to interfere with temozolomide-induced apoptosis by downregulating Bax gene expression. The findings underscore the importance of targeting sialic acid as a therapeutic strategy to overcome chemoresistance in glioma treatment and improve patient outcomes
Keywords: 1321N1, tumor microenvironment, Sialic acid, BAX, Drug resistance