Wang Di, Li Shuheng, Chen Yishan, Luo Jialiang, Li Lei, Wang Bocheng, Xu Yingping, Liang Yunsheng
The First School of Clinical Medicine, Southern Medical University, Guangzhou, China; Dermatology Hospital, Southern Medical University, Guangzhou, China.
Department of Medical Laboratory, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong, China.
J Dermatol Sci. 2023 Feb;109(2):89-98. doi: 10.1016/j.jdermsci.2023.02.002. Epub 2023 Feb 14.
Melanoma is the most common form of skin cancer. Given its high metastasis and high recurrence, its therapies are constantly updated.
The study aims to prove the efficacy of sodium thiosulfate (STS), an antidote to cyanide or nitroprusside poisoning, in melanoma treatment.
We tested the effect of STS by culturing melanoma cells (B16 and A375) in vitro and establishing melanoma mouse models in vivo. The proliferation and viability of melanoma cells were measured by the CCK-8 test, cell cycle assay, apoptosis analysis, wound healing assay, and transwell migration assay. The expression of apoptosis-related molecules, epithelial-mesenchymal transition (EMT)-associated molecules, and the Wnt/β-catenin signaling pathway-related molecules were determined by Western blotting and immunofluorescence.
The high metastasis of melanoma is considered to be linked to the EMT process. The scratch assay using B16 and A375 cells also showed that STS could inhibit the EMT process of melanoma. We demonstrated that STS inhibited the proliferation, viability, and EMT process of melanoma by releasing HS. STS-mediated weakening of cell migration was related to the inhibition of the Wnt/β-catenin signaling pathway. Mechanistically, we defined that STS inhibited the EMT process via the Wnt/β-catenin signaling pathway.
These results suggest that the negative effect of STS on melanoma development is mediated by the reduction of EMT via the regulation of the Wnt/β-catenin signaling pathway, which provides a new clue to treating melanoma.
黑色素瘤是皮肤癌最常见的形式。鉴于其高转移性和高复发性，其治疗方法不断更新。
本研究旨在证明硫代硫酸钠（STS），一种氰化物或硝普钠中毒的解毒剂，在黑色素瘤治疗中的疗效。
我们通过体外培养黑色素瘤细胞（B16和A375）和建立体内黑色素瘤小鼠模型来测试STS的效果。通过CCK-8试验、细胞周期分析、凋亡分析、伤口愈合试验和Transwell迁移试验测量黑色素瘤细胞的增殖和活力。通过蛋白质免疫印迹法和免疫荧光法测定凋亡相关分子、上皮-间质转化（EMT）相关分子以及Wnt/β-连环蛋白信号通路相关分子的表达。
黑色素瘤的高转移性被认为与EMT过程有关。使用B16和A375细胞的划痕试验也表明STS可以抑制黑色素瘤的EMT过程。我们证明STS通过释放HS抑制黑色素瘤的增殖、活力和EMT过程。STS介导的细胞迁移减弱与Wnt/β-连环蛋白信号通路的抑制有关。从机制上讲，我们确定STS通过Wnt/β-连环蛋白信号通路抑制EMT过程。
这些结果表明，STS对黑色素瘤发展的负面影响是通过调节Wnt/β-连环蛋白信号通路减少EMT介导的，这为治疗黑色素瘤提供了新的线索。
