Lee Yoon Jin, Heo Jae Young, Kim Dong Sung, Choi Yu Sung, Kim Sooyoung, Nam Hae Seon, Lee Sang Han, Cho Moon Kyun
Department of Biochemistry, Soonchunhyang University College of Medicine, Cheonan, Korea.
Division of Molecular Cancer Research, Soonchunhyang Medical Research Institute, Soonchunhyang University, Cheonan, Korea.
Ann Dermatol. 2023 Jun;35(3):217-228. doi: 10.5021/ad.22.200.
Recent studies suggest that MEK1/2 inhibitors, including binimetinib, significantly improve malignant melanoma (MM) patient survival. Growing evidence suggests that phytochemicals, especially curcumin, can overcome drug resistance in cancer cells through a variety of mechanisms.
This study aims to examine curcumin's efficacy combined with binimetinib in human MM cells.
We used 2D monolayer and 3D spheroid human epidermal melanocyte culture models, HEMn-MP (human epidermal melanocytes, neonatal, moderately pigmented), and two human MM cell lines, G361 and SK-MEL-2, to evaluate cell viability, proliferation, migration, death, and reactive oxygen species (ROS) production following single therapy treatment, with either curcumin or binimetinib, or a combination of both.
Compared to MM cells treated with single therapy, those with combination therapy showed significantly decreased cell viability and increased ROS production. We observed apoptosis following both single and combination therapies. However only those who had had combination therapy had necroptosis.
Collectively, our data demonstrates that curcumin exerts significant synergistic anticancer effects on MM cells by inducing ROS and necroptosis when combined with binimetinib. Therefore, a strategy of adding curcumin to conventional anticancer agents holds promise for treating MM.
近期研究表明，包括比美替尼在内的MEK1/2抑制剂可显著提高恶性黑色素瘤（MM）患者的生存率。越来越多的证据表明，植物化学物质，尤其是姜黄素，可通过多种机制克服癌细胞的耐药性。
本研究旨在探讨姜黄素联合比美替尼对人MM细胞的疗效。
我们使用二维单层和三维球体人表皮黑素细胞培养模型、HEMn-MP（人表皮黑素细胞，新生儿，中度色素沉着）以及两种人MM细胞系G361和SK-MEL-2，来评估单药治疗（姜黄素或比美替尼）或两者联合治疗后细胞的活力、增殖、迁移、死亡及活性氧（ROS）生成情况。
与单药治疗的MM细胞相比，联合治疗的细胞活力显著降低，ROS生成增加。单药治疗和联合治疗后均观察到细胞凋亡。然而，只有联合治疗组出现了坏死性凋亡。
总体而言，我们的数据表明，姜黄素与比美替尼联合使用时，通过诱导ROS和坏死性凋亡对MM细胞发挥显著的协同抗癌作用。因此，在传统抗癌药物中添加姜黄素的策略有望用于治疗MM。
