Small ubiquitin-related modifiers (SUMO) represent a class of ubiquitin-like proteins that are conjugated, like ubiquitin, by a set of enzymes to form cellular regulatory proteins, and play key roles in the control of cell proliferation, differentiation, and apoptosis. We found that ginkgolic acid (GA) can significantly reduce cell vitality in a dose- and time-dependent manner and can also accelerate cyto-apoptosis in both Tca8113 and Cal-27 cells. Migration and wound-healing assays were executed to determine the anti-migration effect of GA in oral squamous cell carcinoma (OSCC) cell lines. GA represses transforming growth factor-β1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) markers in OSCC cell lines. This investigation is the first evidence that GA suppresses TGF-β1-induced SUMOylation of SMAD4. We show that GA affects the phosphorylation of SMAD2/3 protein and the release of SMAD4. In the xenograft mouse model, the OSCC progression was reduced by GA, effectively suppressing the growth of tumors. In addition, siSMAD4 improved cell migration and viability, which was inhibited by GA in Tca8113 cells. GA suppresses tumorigenicity and tumor progression of OSCC through inhibition of TGF-β1-induced enhancement of SUMOylation of SMAD4. Thus, GA could be a promising therapeutic for OSCC.

小型泛素相关修饰物（SUMO）代表一类泛素样蛋白，它们像泛素一样通过一组酶偶联形成细胞调节蛋白，并在控制细胞增殖，分化和凋亡中发挥关键作用。我们发现银杏酸（GA）可以以剂量和时间依赖性方式显着降低细胞活力，并且还可以加速Tca8113和Cal-27细胞的细胞凋亡。进行迁移和伤口愈合测定法以确定GA在口腔鳞状细胞癌（OSCC）细胞系中的抗迁移作用。GA抑制OSCC细胞系中转化生长因子-β1（TGF-β1）诱导的上皮-间质转化（EMT）标记。这项研究是GA抑制TGF-β1诱导的SMAD4的SUMOylation的第一个证据。我们表明遗传算法影响SMAD2 / 3蛋白的磷酸化和SMAD4的释放。在异种移植小鼠模型中，GA降低了OSCC进展，从而有效地抑制了肿瘤的生长。另外，siSMAD4改善了细胞迁移和生存能力，而GA抑制了Tca8113细胞的迁移和生存能力。GA通过抑制TGF-β1诱导的SMAD4的SUMOylation增强来抑制OSCC的致瘤性和肿瘤进展。因此，GA可能是OSCC的有希望的治疗方法。