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

Abstract

Backgorund: Platinum-based chemo therapeutics are main treatment option for the treatment of ovarium cancer. However, 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 in related to developing resistance against cisplatin. Hence, more effective strategies against drug resistance are essential for the 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 combination effect of chemotherapy and low-intensity ultrasound (LIUS) to overcome the chemo-resistance. Objective: The present study desired the effects of ultrasound (US) + cisplatin (Cis)-based combination therapy was examined to advance an effective treatment against drug resistance in cisplatin-resistant ovarian cancer cells A2780 (A2780cis) in vitro conditions. Methods: 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 separately, 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. Results: In both US parameters, 1 MHz, 1.0 W/cm2, 50% DC, 3 min waveform was shown to be more effective in breaking 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. Conclusion: Ultrasound-based combination therapies show promise in combatting chemoresistance, and the disadvantages of conventional cancer treatments such as cancer recurrence, drug resistance, and financial problems might be reduced by the effectiveness of combination therapy of ultrasound therapy and chemotherapy.

Knowledge mapping and global trends in the field of low-intensity pulsed ultrasound and endocrine and metabolic diseases: a bibliometric and visual analysis from 2012 to 2022

“…High-frequency keywords and burst words help scholars clarify future research directions in related fields. After keyword network and burst word analysis, we found that LIPUS-related research has gradually progressed from previous growth factors (36,37), fracture healing (38)(39)(40)(41), and integrins (42)(43)(44) to fields such as oxidative stress (45), regeneration (46,47), and tumors (48)(49)(50). This suggests that the exploration of molecular biological mechanisms for LIPUS is gradually deepening, and its application areas are gradually expanding to major diseases such as cancer, proving once again the broad application prospects and clinical value of LIPUS.…”

Low-intensity pulsed ultrasound in obstetrics and gynecology: advances in clinical application and research progress

“…Traditional cancer chemotherapy has limitations such as drug resistance and drug side effects. The effectiveness of LIPUS combined with platinum to overcome chemoresistance has been demonstrated in platinum-resistant ovarian cancer cells by measuring cell viability, colony formation, and cell cycle analysis ( 55 ). The principle may be that LIPUS improves cell membrane permeability and intracellular drug concentration increases the therapeutic effect.…”