Study On The Apoptosis Of Osteosarcoma Cell Induced By Combination Of Trail And Celastrol

Objective: To study the inhibition effect of TRAIL combined with Celastrol on the osteosarcoma cell lines so as to explore the new method of the clinical treatment and the potential mechanisms.Methods: TRAIL and Celastrol were used on the U2 OS cells individually or jointly so as to observe their synergistic effects on the apoptosis of osteosarcoma cells.U2 OS cells were treated with certain concentrations of celastrol,and then the cell viability was measured by MTT assay.Apoptosis induction was detected by flow cytometry.The protein expressions of DR4 and DR5 were evaluated by western blotting.Results: Twenty-four hours after the application of 25ng/ml TRAIL and 0.25?mol/l Celastrol jointly on the U2 OS cells,the inhibition rate is 36.47% by MTT essay which is significantly higher than the application of 0.25?mol/l Celastrol(14.26%)and 25ng/mL TRAIL(18.97%)(P<0.01).Morphological changes observed with inverted phase contrast microscope,tumor killing effect of joint application was much stronger than respective application.Celastrol inhibited the growth of human osteosarcoma cells in a time and dose-dependent manner.Besides,it could induce their apoptosis.Celastrol treatment up-regulated the expression of DR4 and DR5 in U2 OS cells.Conclusion: Combination of TRAIL and Celastrol is obviously conducive to killing effect of osteosarcoma cells,which is achieved by inducing apoptosis.Celastrol is able to cause the apoptosis of human osteosarcoma cells through the up-regulation of death receptors(DR4 and DR5).