摘要
目的观察卵巢癌中核因子κB(nuclear factor kappa B,NF-κB)在活化及抑制状态时多药耐药基因1表达产物P-糖蛋白(P-glycoprotein,P-gp)的表达情况,探讨二者之间的关系。方法用多西他赛(Docetaxel)及NF-κB活化抑制剂二硫代氨基甲酸吡咯烷(pyrrolidine dithiocarbamate,PDTC)作用于卵巢癌SKOV-3细胞,Western Blot法分析胞核P65蛋白表达,流式细胞仪检测细胞膜P-gp表达及细胞凋亡,MTT法观察细胞生长抑制。结果单用Docetaxel组胞核P65蛋白、胞膜P-gp表达均增多,加用PDTC可逆转此现象;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(2.5μmol/L、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。结论P-gp表达可能与NF-κB活化有关;抑制NF-κB活化可增强卵巢癌细胞对Docetaxel的敏感性。
Objective To investigate the expression of multidrug resistance gene 1 product P-glycoprotein （P-gp） when nuclear factor kappa B is induced or inhibited. Methods Ovarian cancer cells SKOV-3 were treated with Docetaxel or combinded with pyrrolidine dithiocarbamate （PDTC）, the inhibitor of NF-κB. Western blot assay, flow cytometry assay and MTT assay were used to measure P65 protein, P-gp, apoptosis of cancer cells, and the survival rate respectively. Results Docetaxel increased P65 protein and P-gp expression, while combind use of PDTC reversed this function. Both Docetaxel（ ≥ 1 μg/mL）and PDTC（ ≥ 10μmol/L） significantly inhibited the growth of SKOV-3 cells, and caused apoptosis. The combined use of Docetaxel and PDTC at low concentrations significantly inhibited the growth of cancer cells and caused apoptosis as compared with those treated with Docetaxel only. Conclusion The expression of P-gp may be ralated to the activation of NF-κB; Inhibition of NF-κB can enhance the chemosensitivity of ovarian cancer cells to Docetaxel.
出处
《基础医学与临床》
CSCD
北大核心
2006年第2期187-191,共5页
Basic and Clinical Medicine
