Short-term hyperosmolality pretreatment on cells can reduce the radiosensitivity via RVI and Akt1 activation

Abstract

Background/Aims: The ionizing radiation (IR) has been applied in clinical treatment for many years and the radiosensitivity is crucial to the treatment. Radiosensitivity of cells is subjected to many environmental factors, such as hypoxia and temperature. Hyperosmolality as a common environmental factor has been demonstrated to be associated with survival and apoptosis of cells in many studies. Thus we investigated the influence of hyperosmolality on cells radiosensitivity. Methods: We examined the viability and surviving fraction of L-O2 cells of irradiated L-O2 cells, and detected the effect on AHH-1 cells by flow cytometry, in order to investigate the effect of short-term hyperosmolality pretreatment on cells radiosensitivity. Comet assay was used to assess the DNA strand breaks. Then the detection of Akt1 by western blot and the process of regulatory volume increase by CYSY-TT were involved in the mechanism. Result: We demonstrated that a short-term hyperosmolality pretreatment on cells could reduce their radiosensitivity. Further research indicated that the short-term hypertonic condition could induce regulatory volume increase (RVI), which activated Akt1 and degenerated the IκB-α. This process was associated with reduced cells radiosensitivity. Finally, we used the flufenamic acid (FFA), a blocker to cation channels (HICCs) to inhabit RVI and consequently inhabit the protective effect of hyperosmolality on irradiated cells. Conclusion: a short-term hyperosmolality pretreatment could reduce the cells radiosensitivity by RVI and following activation of Akt1.