Combination of oridonin and TRAIL induces apoptosis in uveal melanoma cells by upregulating DR5  

作　　者：Xin Hua Peng Wu Guo-Sheng Gao Xiao-Lei Ye 

机构地区：[1]Department of Clinical Laboratory,Hwa Mei Hospital,University of Chinese Academy of Sciences,Ningbo 315010,Zhejiang Province,China [2]Ningbo Institute of Life and Health Industry,University of Chinese Academy of Sciences,Ningbo 315010,Zhejiang Province,China [3]Department of Clinical Laboratory,Renmin Hospital of Wuhan University,Wuhan 430060,Hubei Province,China [4]College of Life Sciences,China West Normal University,Nanchong 637009,Sichuan Province,China

出　　处：《International Journal of Ophthalmology(English edition)》2021年第12期1834-1842,共9页国际眼科杂志（英文版）

基　　金：Ningbo Leader and Top Notch Person Training Project(No.20150012).

摘　　要：AIM:To investigate the inhibitory effect of the combined use of tumor necrosis factor-related apoptosis-inducing ligand(TRAIL)and oridonin on choroidal melanoma cell lines,and to explore its underlying mechanism.METHODS:MUM-2B and C918 cells were treated with different concentrations of TRAIL and oridonin,and MTT assay used to evaluate the inhibition rate of the two compounds on cells.Then,the cell cycle distribution and apoptosis were detected by flow cytometry,and changes in apoptosis-related proteins such as death receptor 5(DR5),a-caspase-3,and x-linked inhibitor of apoptosis protein(XIAP)were detected by Western blot.MUM-2B cells were transfected with si-DR5,which interfered with the expression of the DR5 gene.MTT and Western blot assay were used to detect cell activity and apoptosis-related proteins.RESULTS:When TRAIL and oridonin were simultaneously administered to the MUM-2B cells,the apoptosis rate was significantly higher than that by the two drugs individually.However,the effect of combined use of TRAIL and oridonin on C918 cells was not significantly different from that used alone.Cell cycle analysis showed that TRAIL and oridonin could induce G2/M arrest in MUM-2B cells.The Western blot results showed that the protein expression levels of the DR5,a-caspase-3,and BAX increased,while the expression levels of the anti-apoptosis-related proteins XIAP and BCL-2 were suppressed when TRAIL and oridonin simultaneously administered to MUM-2B cells.Interfering the expression of DR5 gene in MUM-2B cells could reverse the inhibitory effect of oridonin and TRAIL on the proliferation and apoptosis induction of MUM-2B cells.CONCLUSION:The inhibitory effects of oridonin and TRAIL on MUM-2B cells are significantly enhanced when they were administered as a combined treatment,which may ascribe to up-regulation of DR5.

关 键 词：tumor necrosis factor-related apoptosisinducing ligand ORIDONIN APOPTOSIS choroidal melanoma 

分 类 号：R285[医药卫生—中药学]