Meng Huijuan, Pang Yunyan, Liu Guoyan, Luo Zengxiang, Tan Haiyang, Liu Xiangming
Department of Dermatology, the Affiliated Hospital of Weifang Medical University, Shandong, China.
Department of Pharmacy, the Affiliated Hospital of Weifang Medical University, Shandong, China.
J Dermatol Sci. 2020 Dec;100(3):201-208. doi: 10.1016/j.jdermsci.2020.10.008. Epub 2020 Oct 17.
JAK2/STAT3 pathway is involved in the development and progression of melanoma once DNA damage is caused by environment and genetic factors.
Here, we aimed to identify novel inhibitor of JAK2/STAT3 pathway and reveal the underlying mechanisms.
Eighty MedChemExpress compounds were screened by using STAT3-Luc reporter in A375 cells. Podocarpusflavone A (PCFA) was identified as an inhibitor of STAT3, which was further verified in four melanoma cell lines. The anti-melanoma effects and mechanism of PCFA were examined and explored in melanoma cells and mouse xenograft models by using Western blot and cell-counting kit-8 assay.
PCFA exhibited potent inhibitory effects on melanoma both in vitro and in vivo. PCFA inhibited the activation of STAT3 through suppressing the phosphorylation of JAK2, and then restrained cell cycle and induced apoptosis of melanoma cells.
PCFA inhibits melanoma growth via the inhibition of JAK2/STAT3 pathway, which provides a promising therapeutic strategies of melanoma treatment.
一旦环境和遗传因素导致DNA损伤，JAK2/STAT3信号通路就会参与黑色素瘤的发生和发展。
在此，我们旨在鉴定JAK2/STAT3信号通路的新型抑制剂，并揭示其潜在机制。
利用STAT3荧光素酶报告基因在A375细胞中筛选80种MedChemExpress化合物。罗汉松黄酮A（PCFA）被鉴定为STAT3的抑制剂，并在四种黑色素瘤细胞系中进一步验证。通过蛋白质免疫印迹法和细胞计数试剂盒-8法在黑色素瘤细胞和小鼠异种移植模型中检测并探究PCFA的抗黑色素瘤作用及其机制。
PCFA在体外和体内均对黑色素瘤表现出强大的抑制作用。PCFA通过抑制JAK2的磷酸化来抑制STAT3的激活，进而抑制细胞周期并诱导黑色素瘤细胞凋亡。
PCFA通过抑制JAK2/STAT3信号通路抑制黑色素瘤生长，这为黑色素瘤治疗提供了一种有前景的治疗策略。
