Mechanism of apoptosis of human osteosarcoma M-G63 induced by arsenic trioxide

Abstract

Objective To observe the apoptosis of osteosarcoma MG-63 cells induced by As₂O₃ and to explore its possible mechanisms. Methods The flowcytometric analysis and transmission electronmicroscope were performed to investigate the inducing apoptosis and inhibitative of As₂O₃ on osteosarcoma MG-63 cells. In order to study mechanism of apoptosis in MG-63 cells treated with As₂O₃, microarray was performed. The down-regulated gene was confirmed by RT-PCR, Northern-blotting. Results After treated with As₂O₃, hypodiploid peak before G0/G1 phase was observed in MG-63 cells through FCM analysis. Loss of microvilli, condensation and fragmentation of nuclear chromatin, condensation of cytoplasmic organelles, dilatation of the endoplasmic reticulum shrinkage of cells and alterations in cell membranes and apoptosis bodies which were observed in MG-63 cells treated with As₂O₃ by transmission electronmicroscope. The results of microarray show that As₂O₃ induced MG-63 cell apoptosis involves down-regulation of IEX-1 and the down-regulated gene is confirmed by RT-PCR and Northern-blotting. Conclusion The results show that As₂O₃ selectively inhibits growth of the solid tumor MG-63 cells by triggering apoptosis and indicates MG-63 induced by As₂O₃ cell apoptosis may through the IEX-1 pathway.

Keywords

arsenic trioxide / osteosarcoma MG-63 / apoptosis / IEX-1

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