二硫代氨基甲酸吡咯烷增敏多西他赛对卵巢癌细胞毒性作用的机制研究  

Pyrrolidine dithiocarbamate enhances chemosensitivity of ovarian cancer cells to docetaxel and its machanism

作　　者：刘国红[1] 王苏荣[1] 王波[1] 

机构地区：[1]山东大学齐鲁医院妇产科,山东济南250012

出　　处：《山东大学学报（医学版）》2006年第3期248-251,共4页Journal of Shandong University:Health Sciences

基　　金：国家自然科学基金资助课题(30271316)

摘　　要：目的:探讨核因子κB(nuclear factor kappa B,NF-κB)活化抑制剂二硫代氨基甲酸吡咯烷(Pyrrolidine Dithiocarbamate,PDTC)对多西他赛(Docetaxel)致卵巢癌SKOV-3细胞毒性作用的影响。方法:用不同浓度PDTC、Docetaxel以不同时间间隔作用于卵巢癌SKOV-3细胞,MTT法观察细胞生长抑制,West-ern Blot法分析胞浆内NF-κB抑制蛋白α(inhibitor of NF-κB,I-κB-α)、胞核P65蛋白表达;流式细胞术检测细胞凋亡。结果:Docetaxel(≥1 mg/L)或PDTC(≥10μmol/L)均明显抑制SKOV-3细胞的生长,引起细胞凋亡;小剂量PDTC(2.5、5μmol/L)和Docetaxel(0.01 mg/L)联合应用与单用Docetaxel比较,可明显抑制细胞生长,增加细胞凋亡率;单用Docetaxel组与对照组比较,胞浆I-κB-α蛋白减少而胞核P65蛋白增多,加用PDTC可逆转此现象。结论:小剂量PDTC可增强卵巢癌细胞对Docetaxel的敏感性,这一作用与PDTC抑制P65蛋白进入核内有关。Objective： To evaluate the effect of nuclear factor kappa B （NF-κB） inhibitor pyrrolidine dithioearbamate （PDTC） on doeetaxel induced eytotoxity in ovarian cancer cells. Methods： MTT assay, Western blot assay and flow eytometry were used to measure the survival rate, I-κB-α and P65 protein, and the apoptosis of SKOV- 3 ovarian cancer cell, following treatment of various concentrations of docetaxel and PDTC at various intervals, respectively. Results： Both docetaxel（ ≥ 1 mg/L） and PDTC（ ≥ 10 μmol/L） significantly inhibited the growth of SKOV- 3 cells and induced the apopotosis, whereas docetaxel combined with PDTC at low concentrations inhibited the growth of cancer cells and induced the apoptosis more significantly than docetaxel alone. Docetaxel causesd reduction in cytoplasmic I-κB-α protein and increase in nuclear P65 protein, while it combined with PDTC reversed this effect. Conclusion： PDTC at low concentrition enhances chemosensitivity of ovarian cancer cells to docetaxel, which is related to its inhibition of P65 protein＇s nuclear translocation.

关 键 词：卵巢肿瘤 多西他赛 二硫代氨基甲酸吡咯烷 核因子-ΚB 细胞凋亡 

分 类 号：R737.31[医药卫生—肿瘤]