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 a 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 result...