The Experiment Study Of Acetaminophen Reduces Human Glioma Cell Line SHG-44 Growth And Increases Radiosensitivity

Objective:To study the effects of acetaminophen(ACE) alone and combinated with radiation on the cell proliferation,cycle distribution and apoptosis of SHG-44 in vitro and to investigate that ACE may prove to be a useful therapeutic agent and radiosensitization in the treatment of human glioma.MethodsrThe H-TDR incorporation was applied to examine the growth inhibition of human glioma cell line SHG-44 treated with ACE,and the subtoxic dose of ACE was chosen to treat the culture to do the radiosesitive experiment.The cells were planted into four groups in random:control group(C),radiation group(R),ACE group(D) and ACE plus radiation group(D+R).ACE's radiosensitivity was measured by clone forming assay.The cell cycle distribution was analysed by Flow Cytometry(FCM).The morphology of the SHG-44 cells apoptosis and apoptosis ratio were observed by Confocal Laser Scanning Microscopy.ResultsrThe 3H-TDR incorporation results showed the growth of SHG-44 cells was inhibit by ACE.When the cells were exposed to ACE at 5 10-4mol/L,5 10-3mol/L,l 10-3mol/L,l 10-2mol/L for 24h,the inhibitory rates(8.68 6.42%,52.26 7.37%,93.28+2.32 %,99.60+0.12%) respectively were positively correlated with the concentration in the media.ACE could inhibit DNA syntheses.The survival curve was drawn based on the results of clone conforming assay,The D+R group's parameters of D0,Dq ,N were smaller than R group's,The DO of R group was 1.4-fold more than D+R group.Cell cycle analysis showed the four groups have the different cell cycle distribution.In C group,most cells were in the G1-S phase,some cells were in the G2 phase;The percentages of the G2/M phase cells in R and D+R groups were significantly more than C group aftertreatment for 12h(P<0.01),but the percentages between R group and D+R group had no different(P>0.05).After treatment for 24h,the percentages of the G2/M phase cells in R group decreased rapidly and having no different with C group(P>0.05),while the percentage in D+R group maintained in high leval and having different with other groups(p<0.01).There were no differences between every two groups after treatment for 48h(p>0.05).The Confocal Laser Scanning Microscopy can observe condensed chromatin,nuclear fragmentation and apoptotic body of SHG-44.The apoptosis ratio(AI) of SHG-44 of four groups were C(19.1 2.7 % ) , R(30.6+5.8%) ?D(22.2 4.2% , D+R(58.3 8.5%) respectively.The AI of R group was higher than C group's(P<0.05) and D+R group's was significantly higher than other groups(P<0.01).Conclusion: l.ACE could inhibit the growth of human glioma cell line SHG-44.The probable mechanism may be ACE can inhibit DNA syntheses.2.Subtoxic dose of ACE increased the sensitivity of the human glioma cell line SHG-44 in culture to ionizing radiation.The mechanism may be block the SHG-44 cells in the G2/M phase of the cell cycle and induce cells apoptosis.3.Taken together.these results suggest that acetaminophen may prove to be a useful therapeutic agent and radiosensitization in the treatment of human malignant glioma.