Department of Dermatology, College of Medicine, Kyung Hee University, Seoul, Republic of Korea.
Department of Dermatology, College of Medicine, Kyung Hee University, Seoul, Republic of Korea.
J Dermatol Sci. 2018 Jun;90(3):357-360. doi: 10.1016/j.jdermsci.2018.02.004. Epub 2018 Feb 8.
Heat shock proteins (Hsps) are chaperone proteins, which are upregulated after various stresses. Hsp90 inhibitors have been investigated as adjuvant therapies for the treatment of melanoma. Thermal ablation could be a treatment option for surgically unresectable melanoma or congenital nevomelanocytic nevi, however, there is a limitation such as the possibility of recurrence.
We evaluated apoptosis in a melanoma cell line treated with the Hsp90 inhibitor 17-Dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), in hyperthermic conditions.
SK-MEL-2 cells were stimulated at 43 °C for 1 h and treated with 0, 0.1 and 1 μM 17-DMAG. We evaluated the cell viability using MTT and apoptosis with HSP 90 inhibitor. We studied the protein expression of AKT, phospho-AKT, ERK, phospho-ERK, MAPK, and phospho-MAPK, caspase 3,7,9, and anti-poly (ADP-ribose) polymerase.
17-DMAG significantly inhibited the proliferation of the SK-MEL-2 cells at 37 °C (0.1 μM: 44.47% and 1 μM: 61.23%) and 43 °C (0.1 μM: 49.21% and 1 μM: 63.60%), suggesting synergism between thermal stimulation and 17-DMAG. 17-DMAG treatment increased the frequency of apoptotic cell populations to 2.17% (0.1 μM) and 3.05% (1 μM) in 37 °C controls, and 4.40% (0.1 μM) and 4.97% (1 μM) in the group stimulated at 43 °C. AKT phosphorylation were activated by thermal stimulation and inhibited by 17-DMAG.
Hsp90 inhibitor treatment may be clinically applicable to enhance the apoptosis of melanoma cells in hyperthermic condition.
热休克蛋白（Hsps）是伴侣蛋白，在各种应激后上调。Hsp90 抑制剂已被研究作为治疗黑色素瘤的辅助治疗。热疗消融可以作为手术不可切除的黑色素瘤或先天性神经黑色素痣的治疗选择，然而，存在着复发的可能性等局限性。
我们评估了在 HSP90 抑制剂 17-DMAG 处理下，在高温条件下黑色素瘤细胞系中的细胞凋亡。
SK-MEL-2 细胞在 43°C 下刺激 1 小时，并用 0、0.1 和 1µM 17-DMAG 处理。我们使用 MTT 评估细胞活力，使用 HSP90 抑制剂评估细胞凋亡。我们研究了 AKT、磷酸化 AKT、ERK、磷酸化 ERK、MAPK 和磷酸化 MAPK、caspase 3、7、9 和多聚（ADP-核糖）聚合酶的蛋白表达。
17-DMAG 显著抑制 SK-MEL-2 细胞在 37°C（0.1µM：44.47%和 1µM：61.23%）和 43°C（0.1µM：49.21%和 1µM：63.60%）的增殖，表明热刺激和 17-DMAG 之间存在协同作用。17-DMAG 处理将细胞凋亡的频率从 37°C 对照组的 2.17%（0.1µM）和 3.05%（1µM）增加到 4.40%（0.1µM）和 4.97%（1µM），在 43°C 刺激组中。AKT 磷酸化被热刺激激活，并被 17-DMAG 抑制。
Hsp90 抑制剂的治疗可能在临床上适用于增强高温条件下黑色素瘤细胞的凋亡。
