Lee Sang Gyu, Lee Dong Gun, Joo Yong Hoon, Chung Namhyun
Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea.
Department of Biosystems and Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea.
Oncol Lett. 2021 Sep;22(3):667. doi: 10.3892/ol.2021.12928. Epub 2021 Jul 14.
Various therapies have been developed to target malignant melanoma, which is associated with a high mortality rate worldwide. Although dacarbazine (DTIC) is employed for treating melanoma, it is associated with several side effects. Hence, patients with melanoma are co-treated with additional drugs to mitigate the side effects of DTIC. In the present study, synergistic therapeutic effects of the DTIC/oxyresveratrol (ORT) combination were examined using the human malignant melanoma WM-266-4 cell line. Treatment with ORT and DTIC inhibited the proliferation of WM-266-4 cells. Compared with those in the ORT- and DTIC-treated groups, the proportion of cells arrested at the S phase, as well as apoptotic rates, were increased in the ORT and DTIC co-treatment group. In WM-266-4 cells, synergistic proliferation-inhibitory activities of the ORT/DTIC combination were assessed based on cell viability and migration, antioxidant capacity, cytokine production, cell cycle arrest, apoptotic rate and protein expression through WST-1 assay, wound healing assay, flow cytometry and western blotting. Furthermore, the expression levels of proteins, including NOTCH, involved in the pathogenesis of solid cancers, such as melanoma, were examined. Overall, the ORT/DTIC combination synergistically promoted cell cycle arrest at the S phase and the apoptosis of WM-266-4 cells. Thus, this combination treatment may serve as a novel therapeutic strategy for treating malignant melanoma.
已经开发出多种针对恶性黑色素瘤的疗法，恶性黑色素瘤在全球范围内与高死亡率相关。尽管达卡巴嗪（DTIC）用于治疗黑色素瘤，但它有几种副作用。因此，黑色素瘤患者会联合使用其他药物来减轻DTIC的副作用。在本研究中，使用人恶性黑色素瘤WM-266-4细胞系检测了DTIC/氧化白藜芦醇（ORT）组合的协同治疗效果。ORT和DTIC处理抑制了WM-266-4细胞的增殖。与ORT和DTIC处理组相比，ORT和DTIC联合处理组中停滞在S期的细胞比例以及凋亡率均增加。在WM-266-4细胞中，通过WST-1检测、伤口愈合检测、流式细胞术和蛋白质印迹法，基于细胞活力和迁移、抗氧化能力、细胞因子产生、细胞周期停滞、凋亡率和蛋白质表达评估了ORT/DTIC组合的协同增殖抑制活性。此外，还检测了包括NOTCH在内的参与黑色素瘤等实体癌发病机制的蛋白质的表达水平。总体而言，ORT/DTIC组合协同促进了WM-266-4细胞在S期的细胞周期停滞和凋亡。因此，这种联合治疗可能成为治疗恶性黑色素瘤的一种新的治疗策略。
