Overcome of Cisplatin Resistance in Ovarian Cancer by Combination of Low-intensity Ultrasound and Cisplatin.

Abstract

Platinum-based chemotherapeutics are the main treatment options for ovarium cancer. However, the development of drug resistance is one of the major issues in chemotherapy. Even targeting a specific pathway may not produce an efficient sensitization to the chemo agent due to various pathways related to developing resistance against cisplatin. Hence, more effective strategies against drug resistance are essential for cancer treatment. In the presence of the ultrasonic waves, increased membrane porosity enables more drug uptake into the cancer cell. Therefore, the promising method in cancer therapy is seen as the use of the combined effect of chemotherapy and low-Intensity Ultrasound (LIUS) to overcome chemoresistance. The present study aimed to examine the effects of Ultrasound (US)+Cisplatin (Cis)- based combination therapy to advance an effective treatment against drug resistance in cisplatinresistant ovarian cancer cells A2780 (A2780cis) under in vitro conditions. Treatment groups as Cis and LIUS with two different ultrasound parameters (10% duty cycle (DC), 1 MHz, 1.0 W/cm2, 1 min and 50% DC, 1 MHz, 1.0 W/cm2, 3 min) were investigated to cope with the chemoresistance in A2780cis. After Cis therapy with IC50 concentrations determined in A2780 and A2780cis, drug-sensitive/resistant ovarian cancer cells were treated by ultrasound. The effects of the US+Cis combination therapy were evaluated by cell viability assays, colony formation, and cell cycle analyses. In both US parameters, the waveform was shown to be more effective in preventing drug resistance. While more than 80% of the cell population was suppressed with the US+Cis combination treatment, more than 90% of the colony formation was suppressed according to the colony formation test results. In addition, US+Cis combination therapy caused different cell cycle arrests in both A2780 and A2780cis cells. Ultrasound-based combination therapies show promising results in combating chemoresistance, and the disadvantages of conventional cancer treatments, such as cancer recurrence, drug resistance, and high cost, might reduce by the effectiveness of combination therapy of ultrasound therapy and chemotherapy.