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细胞周期蛋白依赖性激酶1作为子宫内膜样子宫内膜癌的一种新型治疗靶点。

CDK1 serves as a novel therapeutic target for endometrioid endometrial cancer.

作者信息

Ying Xue, Che Xuan, Wang Jianzhang, Zou Gen, Yu Qin, Zhang Xinmei

机构信息

Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China, 310006.

Jiaxing University Affiliated Women and Children Hospital, Jiaxing, Zhejiang, P.R. China, 314000.

出版信息

J Cancer. 2021 Feb 22;12(8):2206-2215. doi: 10.7150/jca.51139. eCollection 2021.

Abstract

Endometrial cancer (EC) is one of the most common and prevalent gynecologic malignancies worldwide. The aim of this study was to identify a novel therapeutic target for endometrioid endometrial cancer. Bioinformatic analysis was performed and CDK1 was screen out as one of the hub genes in the pathogenesis of EC. Immunohistochemistry was used to verify the expression of CDK1 in endometrial cancer tissue. Cell viability and colony formation were used to study the effects of CDK1 on the proliferation and colony formation of endometrial cancer cells . Apoptosis and cell cycle assays were used to elucidate the mechanism of CDK1 affecting cell proliferation. Tumor xenograft transplantation assay was performed to show the effects of CDK1 on the growth of endometrial cancer cells . CDK1 was over expressed in endometrioid endometrial cancer, and accumulation of cytoplasmic CDK1 was associated with histological grade of EC. CDK1 promoted endometrial cancer cell growth and colony formation . The inhibition of CDK1 activity induced cell apoptosis and caused G2/M phase arrest of cell cycle in endometrial cancer cells. The inhibition of CDK1 activity also inhibited endometrial cancer growth in xenograft models. CDK1 was involved in the pathogenesis of endometrioid endometrial cancer and provided a novel therapeutic target for endometrioid endometrial cancer.

摘要

子宫内膜癌(EC)是全球最常见和普遍的妇科恶性肿瘤之一。本研究的目的是确定子宫内膜样腺癌的一种新的治疗靶点。进行了生物信息学分析,并筛选出CDK1作为EC发病机制中的核心基因之一。采用免疫组织化学法验证CDK1在子宫内膜癌组织中的表达。通过细胞活力和集落形成实验来研究CDK1对子宫内膜癌细胞增殖和集落形成的影响。采用凋亡和细胞周期检测来阐明CDK1影响细胞增殖的机制。进行肿瘤异种移植实验以显示CDK1对子宫内膜癌细胞生长的影响。CDK1在子宫内膜样腺癌中过表达,细胞质CDK1的积累与EC的组织学分级相关。CDK1促进子宫内膜癌细胞生长和集落形成。抑制CDK1活性可诱导细胞凋亡,并导致子宫内膜癌细胞的细胞周期在G2/M期停滞。抑制CDK1活性还可抑制异种移植模型中子宫内膜癌的生长。CDK1参与了子宫内膜样腺癌的发病机制,并为子宫内膜样腺癌提供了一个新的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b29/7974891/8912f9284d46/jcav12p2206g001.jpg

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