The Study Of Growth Inhibition Effect And Radiosensitizing Effect Of Arsenic Trioxide On SHG44 Human Glioma Cells

Objective To investigate the anti-proliferation of arsenic trioxide on Suzhou human glioma cells-44(SHG44); To evaluate the enhancement of radiosensitivity by arsenic trioxide on SHG44 cells in vitro and its mechanism.Methods SHG44 cells were cultured in different concentrations of arsenic trioxide medium in vitro. The inhibitory ratio of the cells were measured by MTT assay. To study the enhancement of radiosensitivity by arsenic trioxide on SHG44 cells, 3^H-TdR incorporation assay has been applied. Assays for apoptosis of the SHG44 cells were performed using AO/EB staining and Annexin V technique. Cell cycle distribution was analyzed by flowcytometry. Intracellular reactive oxygen species(ROS) was detected by using 2',7'-dichlorofluorescein diacetate(DCFH-DA), DNA damage was evaluated by comet assay.Results Arsenic trioxide could cause apoptosis and inhibit the growth of SHG44 cells significantly. The suppression was both in dose-dependence and time-dependence. Arsenic trioxide definitely enhanced radiosensitivity of SHG44 cells. Cell survival experiment showed the decrease of SF₂ and D₀ and increase of Dq when SHG44 cells were irradiated with arsenic trioxide. Apoptosis induced by arsenic trioxide was documented through AO/EB staining and Annexin V technique. DNA flow cytometric analysis indicated that arsenic trioxide could induce rearrangement of cell cycle in SHG44 cells and increase G2-M phase in cells. Compared with those of the control group the intracellular ROS were significantly elevated when cells were treated by arsenic trioxide. The DNA damage of SHG44 cells treated with (60)^Co γ rays, arsenic trioxide and both of them was significantly increased than that of the control group and the DNA damage effect of (60)^Co γ rays associated with arsenic trioxide on the SHG44 cells was stronger than that of radiation or arsenic trioxide only.Conclusion Arsenic trioxide could inhibit the growth of SHG44 cells significantly and might be a potential radiosensitizer for SHG44 cells. Apoptosis, rearrangement of cellcycle and elevation of intracellular ROS caused by arsenic trioxide may be some of the important mechanisms.