title: Ether à go-go 1 silencing in combination with TRAIL overexpression has synergistic antitumor effects on osteosarcoma.
abstract: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been utilized for cancer therapy, but the resistance of cancer cells to TRAIL remains an obstacle. Ether à go-go 1 (Eag1) channel is overexpressed in a variety of cancers and implicated in tumor progression. However, the therapeutic potential of Eag1 in osteosarcoma remains elusive. In this study, we generated CRAd5.TRAIL/siEag1 adenoviral vector that permitted simultaneous knockdown of Eag1 and overexpression of TRAIL and investigated its antitumor effects on human osteosarcoma MG-63 cells. Our results showed that CRAd5.TRAIL/siEag1 induced growth arrest and apoptosis of MG-63 cells in a more efficient manner than CRAd5.TRAIL or CRAd5.siEag1, and had no effect on human osteoblastic hFOB 1.19 cells. Furthermore, treatment of an osteosarcoma xenograft model with CRAd5.TRAIL/siEag1 resulted in significant tumor regression and cancer cell apoptosis, compared with treatment with CRAd5.TRAIL or CRAd5.siEag1. Taken together, our results demonstrate that CRAd5.TRAIL/siEag1 may represent an effective strategy for osteosarcoma gene therapy due to the synergistic antitumor effects of Eag1 knockdown and TRAIL overexpression.
authors.affiliation: Department of Orthopaedics, The Affiliated Southeast Hospital of Xiamen University, Zhangzhou, People's Republic of China.
authors.forename: Jin
authors.initials: J
authors.lastname: Wu
authors.forename: Tian
authors.initials: T
authors.lastname: Zeng
authors.forename: Xinyu
authors.initials: X
authors.lastname: Wu
authors.forename: Quan
authors.initials: Q
authors.lastname: Gao
authors.forename: Wenliang
authors.initials: W
authors.lastname: Zhai
authors.forename: Zhenqi
authors.initials: Z
authors.lastname: Ding
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols; D017209:Apoptosis; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000378:metabolism*; D049109:Cell Proliferation; D004357:Drug Synergism; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020287:In Situ Nick-End Labeling; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D012516:Osteosarcoma / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D051638:Ether-A-Go-Go Potassium Channels; D034741:RNA, Small Interfering; D053221:TNF-Related Apoptosis-Inducing Ligand