Xiao Qing, Ying Jiayi, Qiao Zhuhui, Yang Yiwen, Dai Xiaoxi, Xu Zhongyi, Zhang Chengfeng, Xiang Leihong
Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, PR China.
Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, PR China.
J Dermatol Sci. 2020 Apr;98(1):26-34. doi: 10.1016/j.jdermsci.2020.02.004. Epub 2020 Feb 19.
Melanoma is one of the most aggressive, therapy-resistant skin cancers in the world. Hydrogen sulfide (HS), a newly discovered gasotransmitter, plays a crucial role in the progression and development of many types of cancers. However, the effect of HS on human skin melanoma remains to be elucidated.
We aimed to explore the effect of exogenous HS on melanoma cells and its underlying mechanisms.
In this study, human skin melanoma cell lines, including A375 and SK-MEL-28, were treated with a donor of HS (NaHS). CCK-8, scratch assay, flow cytometric analysis, western blotting and transmission electron microscopy (TEM) were performed to explore the effects of HS on cell behaviors.
Treatment with NaHS inhibited cell proliferation, migration and division, while it could induce cell apoptosis and autophagy in melanoma cell lines. Moreover, NaHS significantly decreased the expression of p-PI3K, p-Akt and mTOR proteins. Furthermore, insulin-like growth factor-1 (IGF-1), the activator of PI3K/AKT/mTOR pathway, could reverse the cell behaviors caused by NaHS.
Our results demonstrated that exogenous hydrogen sulfide could inhibit human melanoma cell development via suppression of the PI3K/AKT/mTOR pathway. Hydrogen sulfide might serve as a potential therapeutic option for melanoma.
黑色素瘤是全球最具侵袭性、对治疗耐药的皮肤癌之一。硫化氢(HS)作为一种新发现的气体信号分子,在多种癌症的进展和发展中起着关键作用。然而,HS对人类皮肤黑色素瘤的影响仍有待阐明。
我们旨在探讨外源性HS对黑色素瘤细胞的影响及其潜在机制。
在本研究中,用人皮肤黑色素瘤细胞系,包括A375和SK-MEL-28,用HS供体(NaHS)处理。进行CCK-8、划痕试验、流式细胞术分析、蛋白质印迹法和透射电子显微镜(TEM)以探讨HS对细胞行为的影响。
用NaHS处理可抑制黑色素瘤细胞系的细胞增殖、迁移和分裂,同时可诱导细胞凋亡和自噬。此外,NaHS显著降低p-PI3K、p-Akt和mTOR蛋白的表达。此外,PI3K/AKT/mTOR途径的激活剂胰岛素样生长因子-1(IGF-1)可逆转由NaHS引起的细胞行为。
我们的结果表明,外源性硫化氢可通过抑制PI3K/AKT/mTOR途径抑制人黑色素瘤细胞的发展。硫化氢可能是黑色素瘤的一种潜在治疗选择。