基于裸鼠模型研究 HI-TOPK-032 对卵巢癌细胞增殖能力的调控作用

doi:10.3969/j.issn.1006-7795.2024.04.008

首都医科大学学报 ›› 2024, Vol. 45 ›› Issue (4): 609-615.doi: 10.3969/j.issn.1006-7795.2024.04.008

• 更年期生殖内分泌与生育力保护 • 上一篇下一篇

基于裸鼠模型研究 HI-TOPK-032 对卵巢癌细胞增殖能力的调控作用

唐帆, 邓梦琪, 苗劲蔚^*

首都医科大学附属北京妇产医院/北京妇幼保健院妇瘤科，北京 100006

收稿日期:2024-05-08 出版日期:2024-08-21 发布日期:2024-07-08
通讯作者: 苗劲蔚 E-mail:jinweimiao@ccmu.edu.cn
基金资助:
北京市医院管理中心“登峰”计划专项项目（DFL20221201）。

The effect of HI-TOPK-032 on the proliferation of ovarian cancer based on a nude mouse model

Tang Fan, Deng Mengqi, Miao Jinwei^*

Department of Gynecologic Oncology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing 100006, China

Received:2024-05-08 Online:2024-08-21 Published:2024-07-08
Supported by:
This study was supported by Beijing Hospitals Authority's Ascent Plan (DFL20221201).

摘要/Abstract

摘要： 目的探讨T-LAK细胞源蛋白激酶/PDZ连接激酶（T-LAK cell-originated protein kinase/PDZ-binding-kinase, TOPK/PBK）在卵巢癌中的表达情况以及TOPK/PBK抑制剂HI-TOPK-032对卵巢癌细胞增殖的影响。方法利用基于基因表达水平值的交互式分析（gene expression profiling interactive analysis，GEPIA）数据库分析TOPK/PBK在卵巢癌与正常卵巢组织中的表达差异。噻唑蓝法（methyl thiazolyl tetrazolium，MTT）细胞活力和增殖检测实验及平板克隆实验分析HI-TOPK-032对OVCAR3及SKOV3细胞增殖能力的影响，构建卵巢癌裸鼠皮下瘤模型验证HI-TOPK-032对卵巢癌瘤体生长能力的影响。结果与正常卵巢组织相比，卵巢癌中TOPK/PBK的表达显著升高（P<0.05）。同时，小分子抑制剂HI-TOPK-032可抑制TOPK/PBK表达，致OVCAR3及SKOV3细胞的增殖能力明显下降（P <0.0001），裸鼠皮下成瘤实验也表明HI-TOPK-032处理组瘤体质量［(0.670±0.450)g vs (1.514±0.358)g ］和体积［（0.418±0.171）cm³ vs（0.973±0.262）cm³］均显著小于对照组。结论 TOPK/PBK在卵巢癌中高表达，TOPK/PBK抑制剂HI-TOPK-032可抑制卵巢癌细胞增殖。这一发现提示TOPK/PBK可能成为卵巢癌的一个新的治疗靶点。

关键词: 卵巢癌, HI-TOPK-032, T-LAK细胞源蛋白激酶/PDZ连接激酶, 细胞增殖

Abstract: Objective To investigate the expression of T-LAK cell-originated protein kinase/PDZ-binding-kinase (TOPK/PBK) in ovarian cancer and the effect of HI-TOPK-032, an inhibitor of TOPK/PBK, on ovarian cancer cells. Methods The expression of TOPK/PBK in ovarian cancer tissue and normal samples were analyzed by gene expression profiling interactive analysis (GEPIA) software. The effect of HI-TOPK-032 on the proliferative activity of ovarian cancer cells was analyzed by methyl thiazolyl tetrazolium (MTT) assay and colony formation assay. The effect of HI-TOPK-032 was also assessed on subcutaneous ovarian tumor in nude mice. Results The expression of TOPK/PBK in ovarian cancer was significantly higher than that in normal ovarian tissue (P<0.05). With the treatment of HI-TOPK-032, the expression of TOPK/PBK was inhibited, and the proliferation capacity of OVCAR3 and SKOV3 cells decreased (P<0.0001). The mass ［(1.514±0.358)g vs (0.670±0.450)g］ and volume ［(0.418±0.171)cm3 vs (0.973±0.262)cm3］ of subcutaneous tumors in the HI-TOPK-032 treatment group were significantly lower than that in the control group. Conclusions TOPK/PBK is highly expressed in ovarian cancer, contributing to the growth of ovarian cancer. HI-TOPK-032 exerts an inhibiting effect on the growth of ovarian cancer.

Key words: ovarian cancer, HI-TOPK-032, T-LAK cell-originated protein kinase/PDZ-binding-kinase, cell proliferation

中图分类号:

R737.31

唐帆, 邓梦琪, 苗劲蔚. 基于裸鼠模型研究 HI-TOPK-032 对卵巢癌细胞增殖能力的调控作用[J]. 首都医科大学学报, 2024, 45(4): 609-615.

Tang Fan, Deng Mengqi, Miao Jinwei. The effect of HI-TOPK-032 on the proliferation of ovarian cancer based on a nude mouse model[J]. Journal of Capital Medical University, 2024, 45(4): 609-615.

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基于裸鼠模型研究 HI-TOPK-032 对卵巢癌细胞增殖能力的调控作用

The effect of HI-TOPK-032 on the proliferation of ovarian cancer based on a nude mouse model

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