Department of Biology and CESAM, University of Aveiro, 3810-193 Aveiro, Portugal.
Int J Mol Sci. 2022 Mar 25;23(7):3586. doi: 10.3390/ijms23073586.
Melanoma is a drug-resistant cancer, representing a serious challenge in cancer treatment. Dacarbazine (DTIC) is the standard drug in metastatic melanoma treatment, despite the poor results. Hyperthermia has been proven to potentiate chemotherapy. Hence, this work analyzed the combined action of hyperthermia and DTIC on A375 and MNT-1 cell lines. First, temperatures between 40 °C and 45 °C were tested. The effect of DTIC on cell viability was also investigated after exposures of 24, 48, and 72 h. Then, cells were exposed to 43 °C and to the respective DTIC IC10 or IC20 of each time exposure. Overall, hyperthermia reduced cell viability, however, 45 °C caused an excessive cell death (>90%). Combinational treatment revealed that hyperthermia potentiates DTIC’s effect, but it is dependent on the concentration and temperature used. Also, it has different mechanisms from the treatments alone, delaying A375 cells at the G2/M phase and MNT-1 cells at the S and G2/M phases. Intracellular reactive oxygen species (ROS) levels increased after treatment with hyperthermia, but the combined treatment showed no additional differences. Also, hyperthermia highly increased the number of A375 early apoptotic cells. These results suggest that combining hyperthermia and DTIC should be more explored to improve melanoma treatment.
黑色素瘤是一种耐药性癌症，是癌症治疗中的一个严重挑战。达卡巴嗪（DTIC）是转移性黑色素瘤治疗的标准药物，尽管疗效不佳。已经证明高热能增强化疗的效果。因此，这项工作分析了高热与 DTIC 对 A375 和 MNT-1 细胞系的联合作用。首先，测试了 40°C 至 45°C 的温度。还研究了 DTIC 在暴露 24、48 和 72 小时后对细胞活力的影响。然后，将细胞暴露于 43°C 和各自的 DTIC IC10 或每个暴露时间的 IC20。总的来说，高热降低了细胞活力，但 45°C 会导致过度的细胞死亡（>90%）。联合治疗表明，高热增强了 DTIC 的效果，但这取决于所使用的浓度和温度。此外，它与单独治疗的机制不同，使 A375 细胞停滞在 G2/M 期，使 MNT-1 细胞停滞在 S 和 G2/M 期。治疗后细胞内活性氧（ROS）水平增加，但联合治疗没有显示出额外的差异。此外，高热大大增加了 A375 早期凋亡细胞的数量。这些结果表明，应该更多地探索将高热与 DTIC 联合使用，以改善黑色素瘤的治疗。
