Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Curr Med Sci. 2024 Jun;44(3):623-632. doi: 10.1007/s11596-024-2877-z. Epub 2024 Jun 10.
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.
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.
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.
CDC20 is a novel molecular target in EC, and Apcin could be developed as a candidate antitumor drug for EC treatment.
子宫内膜癌（EC）是一种常见的妇科恶性肿瘤，其发病率和死亡率呈上升趋势。这突显了寻找新的治疗靶点的迫切需要。细胞分裂周期蛋白 20（CDC20）是一个潜在的治疗靶点，它与肿瘤发生有关。本研究旨在探讨 CDC20 抑制剂 Apcin 对 EC 的影响，并阐明其潜在的作用机制。
采用 CCK8 法和流式细胞术检测 Apcin 对 EC 细胞增殖、凋亡和细胞周期的影响。随后进行 RNA 测序（RNA-seq）以探讨潜在的分子机制，并用 Western blot 和 co-immunoprecipitation 进行验证。进行动物研究以评估体内的抗肿瘤作用。还进行了生物信息学分析，以确定 CDC20 是 EC 的一个潜在治疗靶点。
Apcin 处理抑制了 EC 细胞的增殖并诱导其凋亡，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剂 p21 的上调，p21 被证实与 CDC20 相互作用，从而降低 EC 细胞中下游细胞周期蛋白的表达。体内实验证实 Apcin 处理显著抑制肿瘤生长。与非恶性组织相比，EC 组织中观察到更高的 CDC20 表达，而 EC 患者中 CDC20 表达增加与总生存期和无进展生存期缩短相关。
CDC20 是 EC 的一个新的分子靶点，Apcin 可被开发为 EC 治疗的候选抗肿瘤药物。
