Reversine, or 2-(4-morpholinoanilino)-6-cyclohexylaminopurine, is a 2,6-disubstituted purine derivative. This small molecule shows anti-tumor potential by playing a central role in the inhibition of several kinases related to cell cycle regulation and cytokinesis. In this study, systematic review demonstrated the feasibility and pharmacological mechanism of anti-tumor effect of reversine. Firstly, we grafted MNNG/HOS, U-2 OS, MG-63 osteosarcoma cell aggregates onto chicken embryonic chorioallantoic membrane (CAM) to examine the tumor volume of these grafts after reversine treatment. Following culture, reversine inhibited the growth of osteosarcoma cell aggregates on CAM significantly. experiment, reversine suppressed osteosarcoma cell viability, colony formation, proliferation, and induced apoptosis and cell cycle arrest at G-G phase. Scratch wound assay demonstrated that reversine restrained cell migration. Reversine increased the protein expression of E-cadherin. The mRNA expression of Rac1, RhoA, CDC42, PTK2, PXN, N-cadherin, Vimentin in MNNG/HOS, U-2 OS and MG-63 cells were suppressed and PTEN increased after reversine treatment. Network pharmacology prediction, molecular docking and systematic review revealed MEK1 can be used as an effective target for reversine to inhibit osteosarcoma. Western blot results show the regulation of MEK1 and ERK1/2 by reversine was not consistent in different osteosarcoma cell lines, but we found that reversine significantly inhibited the protein expression of MEK1 in MNNG/HOS, U-2 OS and MG-63. All these suggested that reversine can exert its anti-tumor effect by targeting the expression of MEK1.

中文翻译：

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Reversine通过靶向MEK1抑制人骨肉瘤细胞增殖并诱导细胞凋亡

Reversine 或 2-(4-morpholinoanilinino)-6-cyclohexylaminopurine 是一种 2,6-二取代的嘌呤衍生物。这种小分子通过在抑制与细胞周期调节和胞质分裂相关的几种激酶中发挥核心作用而显示出抗肿瘤潜力。本研究系统评价了逆转录酶抗肿瘤作用的可行性及其药理机制。首先，我们将MNNG/HOS、U-2 OS、MG-63骨肉瘤细胞聚集体移植到鸡胚绒毛尿囊膜（CAM）上，以检查这些移植物在逆素处理后的肿瘤体积。培养后，reversine 显着抑制 CAM 上骨肉瘤细胞聚集体的生长。实验中，逆转素抑制骨肉瘤细胞活力、集落形成、增殖，并诱导细胞凋亡和细胞周期停滞在GG期。划痕试验证明逆向碱抑制细胞迁移。 Reversine 增加 E-钙粘蛋白的蛋白表达。 Reversine处理后，MNNG/HOS、U-2 OS和MG-63细胞中Rac1、RhoA、CDC42、PTK2、PXN、N-cadherin、Vimentin mRNA表达受到抑制，PTEN mRNA表达增加。网络药理学预测、分子对接和系统评价表明MEK1可以作为逆转素抑制骨肉瘤的有效靶点。 Western blot结果显示，reversine对MEK1和ERK1/2的调节在不同的骨肉瘤细胞系中并不一致，但我们发现reversine显着抑制MNNG/HOS、U-2 OS和MG-63中MEK1的蛋白表达。这些都表明reversine可以通过靶向MEK1的表达来发挥抗肿瘤作用。