摘 要 目的: 探讨核因子κB（nuclear factor kappa B， NF-κB）抑制剂二硫代氨基甲酸吡咯烷（pyrrolidine dithiocarbamate,PDTC）提高人卵巢癌SKOV-3细胞对顺铂(cisplatin)化疗敏感性的作用及其可能的机制。方法：用不同浓度PDTC联合顺铂在不同时间作用于卵巢癌SKOV-3细胞，MTT法观察药物作用对细胞生长的抑制，Western Blotting分析胞质内NF-κB 抑制蛋白α（inhibitor of NF-κB ,I-κBα）、胞核P65蛋白的表达；流式细胞术检测细胞凋亡。结果：PDTC（10~40 μmol/L）或顺铂（0.1~100 μg/ml ）均明显抑制SKOV-3细胞的生长(P<0.05或P<0.01)，并引起细胞的凋亡；小剂量PDTC（2.5、5 μmol/L）和顺铂（0.01 μg/ml）联合应用与单用顺铂比较，可明显增加细胞生长抑制率和细胞凋亡率(均P<0.05)。单用顺铂组与对照组比较，胞质I-κBα蛋白减少而胞核P65蛋白增多，联合使用PDTC可逆转此现象。结论：小剂量PDTC可增强卵巢癌细胞对顺铂的敏感性，这一作用可能与PDTC增加I-κBα蛋白的表达而抑制P65蛋白进入核内有关。

Abstract Objective: To determine the promoting effect of pyrrolidine dithiocarbamate (PDTC), an inhibitor of NFκB, on the sensitivity of human ovarian cancer cell line SKOV3 to chemoagent cisplatin and the possible mechanisms. Methods:SKOV3 cells were treated with various concentrations of cisplatin and PDTC combination for different periods. Then the growth inhibition of SKOV3 cells were observed by MTT assay, expression of IκBα and P65 protein by Western blotting assay, and apoptosis of cells by flow cytometry. Results: Separate application of both cisplatin（0.1-10 μg/ml）and PDTC（10-40 μmol/L L）significantly inhibited the growth of SKOV3 cells and caused cell apoptosis(P<0.05 orP<0.01). Even at lower concentration, cisplatin（0.01 μg/ml）combined with PDTC （2.5, 5 μmol/L）resulted more significant growth inhibition and apoptosis of SKOV3 cells than cisplatin alone (both P<0.05). Cisplatin alone reduced cytoplasmic IκBα protein in the cytoplasm and increased nuclear P65 protein compared with control group(both P<0.05), which could be reversed by addition of PDTC. Conclusion: Low dose of PDTC can enhance the chemosensitivity of ovarian cancer cells to cisplatin, which might be related to PDTCinduced IκBα protein and the subsequent inhibition of nuclear translocation of P65 protein.

国家自然科学基金资助项目(No.30271316)