细胞外组蛋白H3通过NF-κB调控膀胱癌细胞增殖及凋亡的作用  

Histone H3 regulates the proliferation and apoptosis of bladder cancer cells through regulating NF-κB

作　　者：韩志军 龙永其 杨帆 舒林飞 李钰琦 HAN Zhijun;LONG Yongqi;YANG Fan;SHU Linfei;LI Yuqi(The First Department of Urology,Zhuzhou Central Hospital,Zhuzhou,Hunan 412007,China;Department of Urology Surgery,the Orthopedics Hospital of Traditional Chinese Medicine of Zhuzhou,Zhuzhou,Hunan 412000)

机构地区：[1]株洲市中心医院泌尿外一科,湖南株洲412007 [2]株洲市中医伤科医院泌尿外科,湖南株洲412000

出　　处：《徐州医科大学学报》2024年第9期652-657,共6页Journal of Xuzhou Medical University

基　　金：湖南省自然科学基金(2018JJ4095);2021年卫生人才“135”工程支持科研项目(株卫函[2021]55号)。

摘　　要：目的 探讨组蛋白H3通过核因子-κB(NF-κB)调控膀胱癌细胞增殖及凋亡的作用及机制。方法 收集手术切除的膀胱癌组织及癌旁组织,培养正常尿路上皮细胞株SV-HUC-1及膀胱癌细胞株BIU-87、J82、RT4、UM-UC-3、T24,检测核蛋白NF-κB、总蛋白生存素(Survivin)的表达水平。T24细胞分组,用不同浓度组蛋白H3(50、100、200 mg/L)、200 mg/L组蛋白H3联合200μmol/L NF-κB抑制剂PDTC处理,检测细胞增殖水平、细胞凋亡率、核蛋白中NF-κB、总蛋白中Survivin、cleaved caspase-9、cleaved caspase-3的表达水平。结果 膀胱癌组织中NF-κB、Survivin的表达水平高于癌旁组织,BIU-87、J82、RT4、UM-UC-3、T24细胞中NF-κB、Survivin的表达水平高于SV-HUC-1细胞(P<0.05);筛选NF-κB、Survivin表达上调最明显的T24细胞进行后续实验;组蛋白H3以浓度依赖的方式增加T24细胞的增殖水平及NF-κB、Survivin的表达水平,抑制T24细胞的凋亡率及cleaved caspase-9、cleaved caspase-3的表达水平(P<0.05);200 mg/L组蛋白H3联合200μmol/L NF-κB抑制剂PDTC处理后,T24细胞的增殖水平及NF-κB、Survivin的表达水平低于200 mg/L组蛋白组,凋亡率及cleaved caspase-9、cleaved caspase-3的表达水平高于200 mg/L组蛋白组(P<0.05)。结论 细胞外组蛋白通过激活膀胱癌细胞中NF-κB/Survivin途径促进细胞增殖、抑制细胞凋亡。Objective To investigate the role and mechanism of histone H3 in regulating the proliferation and apoptosis of bladder cancer cells via nuclear factor-κB(NF-κB).Methods Bladder cancer tissues and adjacent normal tissues were collected after surgical resection.Normal urinary tract epithelial cell line SV-HUC-1 and bladder cancer cell lines BIU-87,J82,RT4,UM-UC-3,and T24 were cultured to detect the levels of nuclear protein NF-κB and total protein Survivin.T24 cells were divided into groups and treated with different concentrations of histone H3(50,100,or 200 mg/L),or a combination of 200 mg/L histone H3 with 200μmol/L NF-κB inhibitor PDTC.The cell proliferation(D 450 value),apoptotic rate,and the levels of NF-κB in the nuclear protein,Survivin in the total protein,and cleaved caspase-9 and cleaved caspase-3 were detected.Results The levels of NF-κB and Survivin in bladder cancer tissues were higher than those in adjacent normal tissues.In BIU-87,J82,RT4,UM-UC-3,and T24 cells,their NF-κB and Survivin levels were higher than those in SV-HUC-1 cells(P<0.05).T24 cells,which showed the most significantly upregulated expression of NF-κB and Survivin,were selected for subsequent experiments.Histone H3 increased the D 450 value and the levels of NF-κB and Survivin in T24 cells in a concentration-dependent manner,and inhibited the apoptotic rate and the levels of cleaved caspase-9 and cleaved caspase-3(P<0.05).After treatment with 200 mg/L histone H3 combined with 200μmol/L NF-κB inhibitor PDTC,their D 450 value and the levels of NF-κB and Survivin in T24 cells decreased,compared with those in the 200 mg/L histone H3 group,while their apoptotic rate and the levels of cleaved caspase-9 and cleaved caspase-3 increased,compared with those in the 200 mg/L histone H3 group(P<0.05).Conclusions Extracellular histone H3 promotes cell proliferation and inhibits apoptosis in bladder cancer cells by activating the NF-κB/Survivin pathway.

关 键 词：膀胱癌 细胞外组蛋白 核因子-ΚB 生存素 增殖 凋亡 

分 类 号：R737.14[医药卫生—肿瘤]