Targeted anti-tumor small molecules are considered to be promising candidates for cancer treatment. The novel diphenyl urea derivative (DUD) was synthesized by the molecular docking based on the structure optimization of Taspine (a natural product). In this study, we explored the anti-metastatic potential of DUD for NSCLC in vitro. DUD significantly suppressed A549 cell migration by reversing EMT. The inhibition was reflected on upregulation of E-cadherin and downregulation of N-cadherin, vimentin, Snail and HIF-1α. Meanwhile, DUD inhibited the β-catenin nuclear translocation by upregulating Axin and downregulating the expression of APC, CK1 and phosphorylation of GSK3β, and simultaneously decreasing MMP9 and MMP13 expression. Moreover, it was associated with the downregulation of the PI3K/Akt/mTOR signaling. Furthermore, we used XAV939, an β-catenin inhibitor, to verify the mechanism of DUD. These results suggested that DUD inhibited A549 cells migration by reversing EMT via Wnt/β-catenin and PI3K/Akt signaling. DUD might be a potential therapeutic drug candidate for NSCLC treatment.

靶向抗肿瘤小分子被认为是癌症治疗的有希望的候选者。基于天然产物Taspine的结构优化，通过分子对接合成了新型二苯基脲衍生物（DUD）。在这项研究中，我们探讨了 DUD 对 NSCLC 的体外抗转移潜力。 DUD 通过逆转 EMT 显着抑制 A549 细胞迁移。这种抑制反映在 E-钙粘蛋白的上调和 N-钙粘蛋白、波形蛋白、Snail 和 HIF-1α 的下调上。同时，DUD通过上调Axin并下调APC、CK1和GSK3β磷酸化的表达，同时降低MMP9和MMP13的表达来抑制β-catenin核转位。此外，它与 PI3K/Akt/mTOR 信号传导的下调有关。此外，我们使用β-catenin抑制剂XAV939来验证DUD的机制。这些结果表明，DUD 通过 Wnt/β-catenin 和 PI3K/Akt 信号传导逆转 EMT，从而抑制 A549 细胞迁移。 DUD 可能是 NSCLC 治疗的潜在候选治疗药物。