Abstract：
Osteosarcoma (OS) is a primary malignant bone tumor that has an abnormal expression of oncogenesis and tumor suppressors and causes dysregulation of various signaling pathways. Thus, novel therapeutic strategies for OS are needed to overcome the resistance of traditional treatments. This study evaluated the cytotoxic and anticancer effects of the association between menadione (MEN) and protocatechuic acid (PCA) in murine OS cells (UMR-106). The concentrations were 3.12 μM of isolated MEN, 500 μM of isolated PCA, and their associations. We performed cell viability assays, morphology modification analysis, cell migration by the wound-healing method, apoptosis by flow cytometry, reactive oxygen species (ROS) production, gene expression of NOX by RT-qPCR, and degradation of MMP-2 and 9 by zymography. Our results showed that the association of MEN+PCA was more effective in OS cells than the compounds alone. The association decreased cell viability, delayed cell migration, and decreased the expression of NOX-2 and ROS. In addition, the MEN+PCA association induced a slight increase in the apoptotic process. In summary, the association can enhance the compound\'s antitumor effects and establish a higher selectivity for tumor cells, possibly caused by significant mitochondrial damage and antioxidant properties.
摘要：
骨肉瘤（OS）是一种原发性恶性骨肿瘤，具有肿瘤发生和肿瘤抑制因子的异常表达，并导致各种信号通路的失调。因此，需要新的OS治疗策略来克服传统治疗的耐药性.这项研究评估了甲萘醌（MEN）和原儿茶酸（PCA）在鼠OS细胞（UMR-106）中的细胞毒性和抗癌作用。浓度为3.12μM的分离MEN，500μM的分离PCA，和他们的协会。我们进行了细胞活力测定，形态改性分析,通过伤口愈合方法进行细胞迁移，通过流式细胞术细胞凋亡，活性氧（ROS）的产生，RT-qPCR检测NOX基因表达,酶谱对MMP-2和9的降解。我们的结果表明，MENPCA的结合在OS细胞中比单独的化合物更有效。这种关联降低了细胞活力，延迟细胞迁移，并降低了NOX-2和ROS的表达。此外,MEN+PCA联合诱导了细胞凋亡过程的轻微增加。总之,这种结合可以增强化合物的抗肿瘤作用，并建立对肿瘤细胞更高的选择性，可能是由显著的线粒体损伤和抗氧化特性引起的。
