Volume-sensitive chloride channels are involved in cisplatin treatment of osteosarcoma

Abstract

Chemotherapy is the most common therapeutic strategy used to treat osteosarcoma. The present study aimed to investigate the effects of functionally activated chloride channels on cisplatin-induced apoptosis of MG-63 human osteosarcoma cells. An MTT assay and flow cytometry were used to detect proliferation and apoptosis of the cells, respectively. Live cell imaging was used to detect volume changes in response to treatment with cisplatin and/or chloride channel blockers. The effects of these treatments on chloride currents were also assayed using the patch-clamp technique. The results of the present study indicate that chloride channel blockers may suppress cisplatin-induced apoptosis. The MG-63 cells cultured with cisplatin demonstrated an apoptotic volume decrease, as well as suppression of cell proliferation; which were reversed by co-treatment with chloride channel blockers. These results suggest that cisplatin may activate chloride channels, and that channel activation is an early signal in the pathways that lead to cisplatin-induced apoptosis and inhibition of proliferation in MG-63 cells. In conclusion, these results indicate that chloride channels have an important role in cisplatin treatment of osteosarcoma.