Mechanism Of TRAIL Tolerance Change After Serum Starvation In Glioma Cells

The mechanism of different resistance to TRAIL with or without serum wasinvestigated preliminary in this work, glioma cells U251and glial tumor cells U87has beenchosen to do it, U251is sensitive to TRAIL while U87is not.However, after serumstarvation, the sensitivity of U251cells decreased, and U87cells increased sensitivity. Inorder to strdy the mechanism, we tested the transcription level, protein level and the changeof promoter activity in different situavation like normal culture, pure TRAIL treatment,serum starvation, unit treatment of serum starvation and TRAIL. Results show thatU251cell lines only high expressed death receptor DR5, which explains the high sensitivityto TRAIL in normal culture, however, after serum starvation, death receptor DR5expression level decreased, it may be the reason for decrease of sensitivity of U251toTRAIL. On the contrary, U87cell is not only high expressing death receptor, but also has ahigh expression of false receptor DcR2, suggesting the high expression of false receptorDcR2is one of the important reasons is not sensitive to TRAIL U87cells, at the same timeafter serum starvation, false receptor DcR2in transcription and expression level havesignificantly reduced, through to the determination of its promoter activity, we also furtherconfirmed the DcR2level lower is likely to be caused by external stimuli promoter activityis reduced, thereby reducing the mRNA transcription, and then make protein expressiondecreased, resulting in U87cells after serum starvation sensitivity to the TRAIL. Inaddition to the attention of TRAIL receptors change, we also tested the change of apoptosisrelated proteins after serum starvation, and found that U87cells which is p53wild-typeincrease the level of pro-apoptotic protein Bax without the change of Bid cleavage,however, U251cells with the mutant p53decrease the cleavage of Bid after starvationcompared with TRAIL alone treatment, which suggest the mechianism with the two cellssource apoptotic pathway activation may different.