Department of Biology and CESAM, University of Aveiro, 3810-193 Aveiro, Portugal.
Int J Mol Sci. 2021 Dec 21;23(1):35. doi: 10.3390/ijms23010035.
Melanoma is the deadliest form of skin cancer, and its incidence has alarmingly increased in the last few decades, creating a need for novel treatment approaches. Thus, we evaluated the combinatorial effect of doxorubicin (DOX) and hyperthermia on A375 and MNT-1 human melanoma cell lines. Cells were treated with DOX for 24, 48, and 72 h and their viabilities were assessed. The effect of DOX IC10 and IC20 (combined at 43 °C for 30, 60, and 120 min) on cell viability was further analyzed. Interference on cell cycle dynamics, reactive oxygen species (ROS) production, and apoptosis upon treatment (with 30 min at 43 °C and DOX at the IC20 for 48 h) were analyzed by flow cytometry. Combined treatment significantly decreased cell viability, but not in all tested conditions, suggesting that the effect depends on the drug concentration and heat treatment duration. Combined treatment also mediated a G2/M phase arrest in both cell lines, as well as increasing ROS levels. Additionally, it induced early apoptosis in MNT-1 cells, while in A375 cells this effect was similar to the one caused by hyperthermia alone. These findings demonstrate that hyperthermia enhances DOX effect through cell cycle arrest, oxidative stress, and apoptotic cell death.
黑色素瘤是皮肤癌中最致命的一种，在过去几十年中，其发病率惊人地增加，这就需要新的治疗方法。因此，我们评估了阿霉素（DOX）和热疗联合应用于 A375 和 MNT-1 人黑色素瘤细胞系的效果。用 DOX 处理细胞 24、48 和 72 小时，评估其活力。进一步分析 DOX IC10 和 IC20（在 43°C 下联合作用 30、60 和 120 分钟）对细胞活力的影响。用流式细胞术分析处理（43°C 下 30 分钟和 DOX 为 IC20 持续 48 小时）对细胞周期动态、活性氧（ROS）产生和细胞凋亡的影响。联合治疗显著降低了细胞活力，但并非在所有测试条件下均如此，这表明这种效果取决于药物浓度和热疗持续时间。联合治疗还导致两种细胞系的 G2/M 期停滞，并增加了 ROS 水平。此外，它诱导了 MNT-1 细胞的早期凋亡，而在 A375 细胞中，这种作用类似于单独热疗引起的作用。这些发现表明，热疗通过细胞周期停滞、氧化应激和凋亡性细胞死亡增强 DOX 的效果。
