title: Proteasome inhibitor MG132 enhances TRAIL-induced apoptosis and inhibits invasion of human osteosarcoma OS732 cells.
abstract: MG132 as a proteasome inhibitor could induce apoptosis in various cancer cells. This study aimed to discuss the effect of proteasome inhibitor MG132 on the TRAIL-induced apoptosis of human osteosarcoma OS732 cells. MG132 and TRAIL were applied on OS732 cells respectively or jointly. Cell survival rates, changes of cellular shape, cell apoptosis and cell invasion were analyzed, respectively, by 3-(4,5)-dimethylthiahiazo(-z-y1)-2,5-di-phenytetrazoliumromide (MTT) assay, inverted phase contrast microscope, flow cytometry, and transwell invasion chamber methods. The protein levels of DR5, caspase-3, caspase-8, p27(kip1) and MMP-9 were measured by Western blot analysis. The results indicated that combination of MG132 and TRAIL had the effect of up-regulating expression of DR5, caspase-3, caspase-8 and p27(kip1), down-regulating expression of MMP-9 and inducing apoptosis as well as suppressing the ability of invasion of OS732 cells. The survival rate of combined application of 10 μM MG132 and 100 ng/ml TRAIL on OS732 cells was significantly lower than that of the individual application (p<0.01). Changes of cellular shape and apoptotic rates also indicated the apoptosis-inducing effect of combined application was much stronger than that of individual application. Cell cycle analysis showed combination of MG132 and TRAIL mostly caused OS732 cells arrested at G2-M-phase. The invasion ability of OS732 cells was restrained significantly in the combined group compared with the individual group and control group.
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning, PR China.
authors.forename: Xiucheng
authors.initials: X
authors.lastname: Li
authors.forename: Tao
authors.initials: T
authors.lastname: Huang
authors.forename: Guangjian
authors.initials: G
authors.lastname: Jiang
authors.forename: Weihua
authors.initials: W
authors.lastname: Gong
authors.forename: Hao
authors.initials: H
authors.lastname: Qian
authors.forename: Chunping
authors.initials: C
authors.lastname: Zou
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004357:Drug Synergism; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology*; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000517:prevention & control*; D012516:Osteosarcoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D061988:Proteasome Inhibitors / Q000494:pharmacology*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D007976:Leupeptins; D061988:Proteasome Inhibitors; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; D053148:Caspase 3; D053181:Caspase 8; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde
keywords: Apoptosis; Invasion; MG132; Osteosarcoma; TRAIL