目的:子宫内膜癌(EC)是一种常见的妇科恶性肿瘤,其特点是发病率和死亡率不断增加。这强调了对新型治疗靶标的关键需求。一个这样的潜在目标是细胞分裂周期20(CDC20),这与肿瘤发生有关。这项研究调查了CDC20抑制剂Apcin对EC的作用,并阐明了所涉及的潜在机制。
方法:Apcin对EC细胞增殖的影响,凋亡,使用CCK8测定和流式细胞术评估细胞周期。随后进行RNA测序(RNA-seq)以探索潜在的分子机制,随后进行Western印迹和免疫共沉淀以验证结果。进行动物研究以评估体内抗肿瘤作用。还进行了生物信息学分析以鉴定CDC20作为EC中的潜在治疗靶标。
结果:用Apcin处理抑制EC细胞增殖并诱导其凋亡,导致细胞周期停滞。用Apcin处理后,与凋亡和细胞周期相关的途径被激活。值得注意的是,Apcin处理导致细胞周期调节因子p21上调,其被证实与CDC20相互作用并因此降低EC细胞中下游细胞周期蛋白的表达。体内实验证实Apcin治疗显著阻碍肿瘤生长。在EC组织中观察到比在非恶性组织中更高的CDC20表达,EC患者CDC20表达增加与总生存期和无进展间期缩短相关。
结论:CDC20是一种新型的EC分子靶标,Apcin可作为治疗EC的候选抗肿瘤药物。
OBJECTIVE: Endometrial carcinoma (EC) is a prevalent gynecological malignancy characterized by increasing incidence and mortality rates. This underscores the critical need for novel therapeutic targets. One such potential target is cell division cycle 20 (CDC20), which has been implicated in oncogenesis. This study investigated the effect of the CDC20 inhibitor Apcin on EC and elucidated the underlying mechanism involved.
METHODS: The effects of Apcin on EC cell proliferation, apoptosis, and the cell cycle were evaluated using CCK8 assays and flow cytometry. RNA sequencing (RNA-seq) was subsequently conducted to explore the underlying molecular mechanism, and Western blotting and coimmunoprecipitation were subsequently performed to validate the results. Animal studies were performed to evaluate the antitumor effects in vivo. Bioinformatics analysis was also conducted to identify CDC20 as a potential therapeutic target in EC.
RESULTS: Treatment with Apcin inhibited proliferation and induced apoptosis in EC cells, resulting in cell cycle arrest. Pathways associated with apoptosis and the cell cycle were activated following treatment with Apcin. Notably, Apcin treatment led to the upregulation of the cell cycle regulator p21, which was verified to interact with CDC20 and consequently decrease the expression of downstream cyclins in EC cells. In vivo experiments confirmed that Apcin treatment significantly impeded tumor growth. Higher CDC20 expression was observed in EC tissue than in nonmalignant tissue, and increased CDC20 expression in EC patients was associated with shorter overall survival and progress free interval.
CONCLUSIONS: CDC20 is a novel molecular target in EC, and Apcin could be developed as a candidate antitumor drug for EC treatment.