Ultrasound increases DNA damage attributable to cisplatin in cisplatin-resistant human ovarian cancer cells.

Abstract

An increased capacity for DNA repair plays a very important role in cisplatin (DDP) resistance in ovarian cancers. Ultrasound is a potential chemotherapy sensitizer. The aim of this study was to determine whether ultrasound in conjunction with chemotherapy increases DNA damage in chemoresistant human ovarian cancer cells. Ultrasound and/or cyclosporin A were used to overcome chemoresistance in a DDP-resistant human ovarian cancer cell line, COC1/DDP. DNA damage was quantified by comet assay, a form of single-cell gel electrophoresis in which the length of the comet tail reflects the level of DNA damage. Neither ultrasound nor cyclosporin A alone led to detectable DNA breakage. The use of ultrasound increased DNA breakage due to DDP, while the use of cyclosporin A did not. The addition of ultrasound and cyclosporin A in conjunction with DDP resulted in a 2.55 times increase in the length of comet tail compared with using DDP alone, while their combined use resulted in a 1.73 times increase compared with the combination of just DDP and insonation. Insonation increases DNA breakage attributable to DDP in chemoresistant human ovarian cancer cells, and might sensitize cyclosporin A.