Ultrasound sensitizes chemotherapy in chemoresistant ovarian cancers
Chemotherapy resistance is still a great challenge to the management of ovarian cancers. Using SKOV3/ADR or COC1/DDP subline as a model of adriamycin- or cisplatin-resistance, ultrasonic chemosensitization was investigated. The addition of noncytotoxic insonation led to a higher cell-death rate as compared with a drug alone. Ultrasound sensitized chemotherapy via increasing intracellular drug accumulation, enhancing drug-induced apoptosis and decreasing the threshold dose for cell apoptosis/necrosis. Ultrasound exposure enhanced cisplatin-induced DNA breakages in COC1/DDP cells but did not decrease the level of glutathione-S-transferase. Chemosensitization attributable to insonation was mostly mediated by cavitation. Ultrasonic chemotherapy had the property of a targeted treatment, in that the dose-anticancer effect and dose-toxicity curves differed from those in conventional chemotherapy. The findings indicated that ultrasound was a non-drug modality for sensitizing chemotherapy in refractory ovarian cancers.
Key words: Chemoresistance, ovarian cancer, ultrasound, sonochemotherapy, targeted therapy.