The Use Of Ultrasound Enhances DNA Breakages Attributable To Cisplatin In Chemoresistant Human Ovarian Cancer Cells

BACKGROUND AND OBJECTIVESOvarian cancer is the leading cause of death in gynecological tumors, and platinum is the first line treatment regime. Chemotherapy resistance frequently occurs and leads to the failure of treatment. Cisplatin (DDP)- resistance is usually mediated by the increase of DNA repair. Our previous investigations have manifested that ultrasound overcame DDP-resistance in human ovarian cancer. The aim of this study was to determine mechanisms from the perspective of DNA breakages.METHODSChemoresistant human ovarian cancer cell line COC1/DDP was used. The experiment was performed in seven groups: (1) group control; (2) group DDP, cells were subjected to DDP; (3) group US, cells were insonated; (4) group DDP+US, cells were exposed to ultrasound after adding DDP; (5) group DDP+CSA, cells were treated by the combination of DDP and cyclosporin A (CSA); (6) group CSA, cells were exposed to CSA; (7) group DDP+CSA+US, cells were treated as that in group DDP+ CSA, and ultrasound was also employed. The level of DNA damages was determined with a comet assay, and ERCC1 with RT-PCR.RESULTSNeither ultrasound nor CSA led to detectable DNA breakages. Ultrasound enhanced DNA breaks due to DDP, and CSA did not potentiate DDP. The combination of ultrasound and CSA resulted in 1.55- and 0.73- fold increments of the length of comet tail, compared with those due to DDP and to the co-use of DDP and insonation, respectively. RT-PCR did not confirmed that ERCC1 was down-regulated.CONCLUSIONUltrasound enhanced DNA damages due to cisplatin in chemoresistant human ovarian cancer cells, which was involved in chemosensitization.