Role of cell division cycle associated 2 in ovarian cancer: Effects on tumor progression and cisplatin resistance.

IF 2.2 4区医学 Q2 PATHOLOGY

Cytojournal Pub Date : 2025-09-10 eCollection Date: 2025-01-01 DOI:10.25259/Cytojournal_59_2025

Yanyan Jin, Xueyun Xu, Wei Li

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引用次数: 0

Abstract

Objective: Ovarian cancer is a disease that seriously endangers the health and life safety of women. At present, no effective preventive and therapeutic measures are available. This study probed the impact of cell division cycle-associated 2 (CDCA2) on ovarian cancer development and cisplatin sensitivity, which provides a new research direction for the study of ovarian cancer.

Material and methods: The protein expression level of CDCA2 was tested by Western blot assay. Cell proliferation was evaluated by cell cloning formation assay and Celigo cell counting. Cell invasion and migration were assessed by Transwell assay. An experiment for nude mouse tumor formation was conducted to analyze the influence of CDCA2 knockdown on tumor growth in vivo. We treated CDCA2 knockdown cells with gradient cisplatin and measured cell viability using the cell counting kit-8 assay. Apoptosis and DNA damage induced by CDCA2 knockdown were investigated by flow cytometry and histone family member X (H2AX) phosphorylated on Ser 139 (γ-H2AX) immunofluorescence, respectively.

Results: CDCA2 expression was knocked down in A2780 and SKOV3 cells. After CDCA2 knockdown, cell proliferation, migration, and invasion ability decreased significantly, and tumor growth in vivo was also limited (P < 0.01). The phosphorylation levels of protein kinase B (AKT) and mechanistic target of rapamycin (mTOR) were reduced by CDCA2 knockdown (P < 0.01), but the effect was reversed by the AKT activator SC-79 (P < 0.01). Knockdown of CDCA2 increased the cisplatin sensitivity of ovarian cancer cells by enhancing apoptosis and DNA damage (P < 0.01).

Conclusion: CDCA2 knockdown inhibited the development of ovarian cancer through the AKT/mTOR pathway and enhanced cisplatin sensitivity. CDCA2 is a potential target to reverse cisplatin resistance in ovarian cancer. It can also be used as a new research direction for the development of ovarian cancer therapy.

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细胞分裂周期相关2在卵巢癌中的作用：对肿瘤进展和顺铂耐药性的影响。

目的：卵巢癌是一种严重危害妇女健康和生命安全的疾病。目前，尚无有效的预防和治疗措施。本研究探讨细胞分裂周期相关2 （CDCA2）对卵巢癌发展和顺铂敏感性的影响，为卵巢癌的研究提供新的研究方向。材料与方法：采用Western blot法检测CDCA2蛋白表达水平。采用细胞克隆形成法和Celigo细胞计数法观察细胞增殖情况。Transwell法检测细胞的侵袭和迁移。通过裸鼠肿瘤形成实验，分析CDCA2敲低对体内肿瘤生长的影响。我们用梯度顺铂处理CDCA2敲低细胞，并使用细胞计数试剂盒-8测定细胞活力。流式细胞术和组蛋白家族成员X （H2AX）在Ser 139 （γ-H2AX）免疫荧光上磷酸化分别研究了CDCA2敲低诱导的细胞凋亡和DNA损伤。结果：CDCA2在A2780和SKOV3细胞中表达下调。CDCA2敲低后，细胞增殖、迁移和侵袭能力显著降低，体内肿瘤生长也受到限制（P < 0.01）。CDCA2敲低可降低蛋白激酶B （AKT）和雷帕霉素（mTOR）的磷酸化水平（P < 0.01），但AKT激活剂SC-79可逆转这一作用（P < 0.01）。敲低CDCA2通过增强细胞凋亡和DNA损伤增加卵巢癌细胞对顺铂的敏感性（P < 0.01）。结论：CDCA2敲低可通过AKT/mTOR通路抑制卵巢癌的发展，增强顺铂敏感性。CDCA2是逆转卵巢癌顺铂耐药的潜在靶点。它也可以作为卵巢癌治疗发展的一个新的研究方向。

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来源期刊

Cytojournal PATHOLOGY-

CiteScore

2.20

自引率

42.10%

发文量

审稿时长

>12 weeks

期刊介绍： The CytoJournal is an open-access peer-reviewed journal committed to publishing high-quality articles in the field of Diagnostic Cytopathology including Molecular aspects. The journal is owned by the Cytopathology Foundation and published by the Scientific Scholar.