[Comparison of the effect of DNA aptamers U31, GR20, GR200 and their combination with radiation therapy on the viability of human glioblastoma cells G22 and Sus\fP2].

Abstract

Aptamers can increase human glioblastoma cell death rate after exposure to radiotherapy. Cell cultures derived from human glioblastomas allow for selection of effective combined therapy.

Objective: To analyze viability of human glioblastoma cell cultures exposed to EGFR-specific aptamers U31, GR20, and GR200 compared to combination of these aptamers and radiotherapy (20 Gy).

Methodology: G22 and Sus\fP2 cell cultures were harvested from tumor tissue. They were exposed to aptamers (10 μM, 72 hours) and irradiated once with 20 Gy. We analyzed viability using flow cytometry.

Results: In G22 cell culture, aptamer U31 reduces apoptosis by 45.8%, but increases necrosis by 67.5%, while GR20 and GR200 increase two types of death (apoptosis and necrosis). In Sus\fP2 culture, all three aptamers significantly increased apoptosis while proportion of necrosis decreased. The most significant decrease in the number of necrotic cells was observed for aptamer U31 (by 77.7%). Radiotherapy combined with aptamers was followed by the following effects for G22 cell culture: U31 and GR200 enhance apoptosis (by 59.4%) and necrosis (by 57.7%), aptamer GR20 increases necrosis by 28.3%. In Sus\fP2 culture, U31 aptamer enhances apoptosis by 132.9% and necrosis by 52.9%, GR20 - 125.4% and 17.7%, GR200 - 27.4% and 30.6%, respectively.

Conclusion: Aptamers have different effects on glioblastoma cell cultures. For Sus\fP2, a combination of radiotherapy with GR20 aptamer is optimal. Either a single application of U31 aptamer or combination of radiotherapy and GR200 aptamer is optimal for G22 cell culture. This result demonstrates the importance of combined therapy and preliminary studies in cell cultures for individualized approach to each CNS tumor.