Department of Pharmacy, School of Basic Medical Sciences, Henan University of Science and Technology, Luoyang 471023, China.
Department of Pharmacy, School of Basic Medical Sciences, Henan University of Science and Technology, Luoyang 471023, China.
Toxicol In Vitro. 2022 Oct;84:105456. doi: 10.1016/j.tiv.2022.105456. Epub 2022 Aug 17.
Targeted Wnt/β-catenin pathway is considered to be a promising therapy for cancer metastasis. The novel O -(2,4-dinitrophenyl) diazeniumdiolate (JS-K) plays a potent inhibitory role in the proliferation of cancers. In this study, HepG2 and SMMC7721 were used to clarify the efficacy of JS-K inhibition of HCC metastasis. JS-K significantly inhibited cell motility through a wound-healing assay and restrained cell migration and invasion at noncytotoxic concentrations. However, the inhibitory effects of migration and invasion were abolished after the addition of NO scavenger, Carboxy-PTIO. In addition, JS-K inhibited the Wnt/β-catenin pathway by a decrease of p-GSK-3β at Ser9, cytosolic β-catenin, and nuclear β-catenin accumulation whereas an increase of p-β-catenin. Furthermore, the transcription regulators c-Myc, survivin, and Cyclin D1 were down-regulated after treating with JS-K. The inhibitory of the Wnt/β-catenin pathway was reversed after the addition of Carboxy-PTIO or LiCl. Meanwhile, JS-K also inhibited the epithelial-mesenchymal transition (EMT)-mediated cell migration and invasion. The characteristics of the inhibition were reflected by the upregulation of E-cadherin whereas the downregulation of Vimentin, Snail, and Slug. Taking together, these results demonstrated that JS-K inhibited HepG2 and SMMC7721 cells migration and invasion by reversing EMT via the Wnt/β-catenin pathway.
靶向 Wnt/β-连环蛋白途径被认为是癌症转移的一种有前途的治疗方法。新型 O-(2,4-二硝基苯基)重氮二酸盐 (JS-K) 在癌症增殖中发挥强大的抑制作用。在这项研究中，HepG2 和 SMMC7721 被用于阐明 JS-K 抑制 HCC 转移的功效。JS-K 通过划痕愈合试验显着抑制细胞迁移，并在非细胞毒性浓度下抑制细胞迁移和侵袭。然而，在用 NO 清除剂 Carboxy-PTIO 处理后，迁移和侵袭的抑制作用被消除。此外，JS-K 通过降低 p-GSK-3β 在 Ser9、细胞质 β-连环蛋白和核 β-连环蛋白积累而抑制 Wnt/β-连环蛋白途径，同时增加 p-β-连环蛋白。此外，JS-K 处理后转录调节剂 c-Myc、survivin 和 Cyclin D1 下调。在用 Carboxy-PTIO 或 LiCl 处理后，Wnt/β-连环蛋白途径的抑制作用被逆转。同时，JS-K 还抑制了上皮-间充质转化 (EMT) 介导的细胞迁移和侵袭。抑制特征反映在 E-钙粘蛋白的上调，而 Vimentin、Snail 和 Slug 的下调。总之，这些结果表明，JS-K 通过逆转 EMT 抑制 HepG2 和 SMMC7721 细胞的迁移和侵袭，通过 Wnt/β-连环蛋白途径。
