未经证实:胃癌是世界范围内发病率最高的癌症之一,死亡率高,预后差。MYC癌基因过度表达是胃癌发生的关键事件,已知其蛋白正调控CDC25B的表达,反过来,在细胞分裂周期进程中起着至关重要的作用。Menadione是维生素K的合成形式,可作为磷酸酶CDC25家族的特异性抑制剂。
UNASSIGNED:为了更好地了解甲萘醌在胃癌中的作用机制,我们评估了其在细胞系和Sapajusapella中的分子和细胞效应,来自新世界的非人灵长类动物具有由N-甲基-N-亚硝基脲诱导的胃癌发生。我们通过蛋白质印迹和RT-qPCR测试了CDC25B的表达。体外测定包括增殖,迁移,侵袭和流式细胞术分析细胞周期停滞。在体内实验中,除了表达分析,我们通过超声检查追踪肿瘤前病变和肿瘤进展,内窥镜检查,活检,组织病理学和免疫组织化学。
UNASSIGNED:我们的试验证明甲萘醌在体内和体外都能降低CDC25B的表达。它能够减少移民,侵袭和增殖率,并诱导胃癌细胞系的细胞周期停滞。此外,我们的体内实验证明甲萘醌抑制肿瘤的发展和进展.
未经批准:我们建议该化合物可能是治疗胃癌的化学疗法的重要药物。此外,CDC25B已被证明是研究和开发这种恶性肿瘤的新治疗策略的有效靶标。
UNASSIGNED: Gastric cancer is one of the most incident types of cancer worldwide and presents high mortality rates and poor prognosis. MYC oncogene overexpression is a key event in gastric carcinogenesis and it is known that its protein positively regulates CDC25B expression which, in turn, plays an essential role in the cell division cycle progression.
Menadione is a synthetic form of vitamin K that acts as a specific inhibitor of the CDC25 family of phosphatases.
UNASSIGNED: To better understand the
menadione mechanism of action in gastric cancer, we evaluated its molecular and cellular effects in cell lines and in Sapajus apella, nonhuman primates from the new world which had gastric carcinogenesis induced by N-Methyl-N-nitrosourea. We tested CDC25B expression by western blot and RT-qPCR. In-vitro assays include proliferation, migration, invasion and flow cytometry to analyze cell cycle arrest. In in-vivo experiments, in addition to the expression analyses, we followed the preneoplastic lesions and the tumor progression by ultrasonography, endoscopy, biopsies, histopathology and immunohistochemistry.
UNASSIGNED: Our tests demonstrated
menadione reducing CDC25B expression in vivo and in vitro. It was able to reduce migration, invasion and proliferation rates, and induce cell cycle arrest in gastric cancer cell lines. Moreover, our in-vivo experiments demonstrated
menadione inhibiting tumor development and progression.
UNASSIGNED: We suggest this compound may be an important ally of chemotherapeutics in the treatment of gastric cancer. In addition, CDC25B has proven to be an effective target for investigation and development of new therapeutic strategies for this malignancy.