Department of Biomedical Engineering, Faculty of Engineering, Erciyes University, 38039, Kayseri, Turkey.
Nanothera Lab, Drug Application and Research Center (ERFARMA), Erciyes University, 38280 Kayseri, Turkey.
Curr Drug Deliv. 2023;20(9):1380-1390. doi: 10.2174/1567201819666220627100857.
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/cm, 1 min and 50% DC, 1 MHz, 1.0 W/cm, 3 min) were investigated to cope with the chemoresistance in A2780cis. After Cis therapy with IC 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.
铂类化疗药物是卵巢癌的主要治疗选择。然而，耐药性的发展是化疗中的主要问题之一。即使针对特定途径进行靶向治疗，由于与顺铂耐药性相关的各种途径，也可能无法使化疗药物有效增敏。因此，对于癌症治疗来说，更有效的耐药性应对策略是必不可少的。在超声波的存在下，增加细胞膜的通透性，使更多的药物进入癌细胞。因此，在癌症治疗中，一种有前途的方法是利用化疗和低强度超声（LIUS）的联合作用来克服化疗耐药性。
本研究旨在探讨超声（US）+顺铂（Cis）联合治疗对体外顺铂耐药卵巢癌细胞 A2780（A2780cis）的耐药性的影响。
研究了 Cis 和两种不同超声参数（10%占空比（DC）、1 MHz、1.0 W/cm、1 分钟和 50% DC、1 MHz、1.0 W/cm、3 分钟）的 LIUS 的联合治疗，以应对 A2780cis 的化疗耐药性。在确定了 A2780 和 A2780cis 中的 IC 浓度后，用 Cis 治疗药物敏感/耐药性卵巢癌细胞，然后用超声处理。通过细胞活力测定、集落形成和细胞周期分析评估 US+Cis 联合治疗的效果。
在这两种超声参数中，波形显示出在预防耐药性方面更有效。在 US+Cis 联合治疗后，超过 80%的细胞群体被抑制，而根据集落形成试验结果，超过 90%的集落形成被抑制。此外，US+Cis 联合治疗导致了 A2780 和 A2780cis 细胞的不同细胞周期停滞。
基于超声的联合治疗在对抗耐药性方面显示出有希望的结果，并且超声治疗和化疗联合治疗的有效性可能会降低传统癌症治疗方法（如癌症复发、耐药性和高成本）的缺点。
