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


METHODS
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.


RESULTS
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.


CONCLUSIONS
Insonation increases DNA breakage attributable to DDP in chemoresistant human ovarian cancer cells, and might sensitize cyclosporin A.
Yu
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T
Laboratory of Biomedical Ultrasonics, Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu, China. yutinghe@hotmail.com
Yang
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Y
Liu
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S
Yu
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D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use*; D020552:Comet Assay; D004249:DNA Damage; D004260:DNA Repair; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000235:genetics / Q000628:therapy*; D014464:Ultrasonic Therapy
D000970:Antineoplastic Agents; D002945:Cisplatin