Synergistic effects of Arsenic trioxide and Radiation: triggering of intrinsic pathway of apoptosis

Purpose: Glioblastoma is the most common brain tumors. Despite multimodality treatment, the median survival of the patients is < 10 -12 months. Arsenic trioxide (ATO) has been reported as an effective anti-cancer and FDA approved drug for treatment of some cancers. The aim of this29study was to determine the underlying apoptosis molecular and cellular mechanisms of arsenic trioxide (ATO) in the presence or absence of ionizing radiation (IR) in vitro in the GBM cell line, U87MG.Material and methods: cells were treated by ATO in different concentrations either in presence or absence of a 4 GY 6-MV X-ray. Viability and apoptosis pathway of both treated and control groups were evaluated using MTT assay and expression analysis of Bax, Bcl-2 and caspase-3 genes and microscopic study, respectively. All experiments were performed on 100μm spheroids.Results: Results showed a significant reduction in cells survival in all treated groups. As expected, the combination treatment was more effective and cell survival was much less in combination treatment than treatment with only ATO. Moreover, ATO and more strongly combined with IR made Bax and caspase-3 up-regulated and bcl-2 down-regulated.Conclusion: We found that ATO and radiation have a synergistic apoptotic effect on glioblastoma multiforme Spheroids by up-regulating of caspase-3 and alteration of the Bax-Bcl-2 balance. Current findings suggest that ATO may act as an anti-cancer agent against GBM cells through triggering of the mitochondrial pathway of apoptosis.

کلیدواژه ها:

Arsenic trioxide ، Radiation ، Apoptosis ، Glioblastoma Multiforme