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

作　　者：唐帆 邓梦琪 苗劲蔚[1] 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)

机构地区：[1]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

出　　处：《首都医科大学学报》2024年第4期609-615,共7页Journal of Capital Medical University

基　　金：北京市医院管理中心“登峰”计划专项项目(DFL20221201)。

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)cm^(3) vs(0.973±0.262)cm^(3)]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。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)cm^(3) vs(0.973±0.262)cm^(3)]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.

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 

分 类 号：R737.31[医药卫生—肿瘤]