NS-398协同顺铂作用人肺腺癌差异蛋白质组分析

背景与目的 实验证明一种高度选择性的COX-2抑制剂--NS-398能增强传统化疗药物顺铂对肺腺癌细胞的生长抑制作用,但其机制尚不清楚.本研究的目的是探讨NS-398与顺铂协同抑制肺腺癌细胞增殖的作用机制.方法 采用二维聚丙烯酰胺凝胶电泳分离NS-398和顺铂作用下肺腺癌细胞的蛋白质,质谱分析法(MALDI-TOF-MS)和数据库查询鉴定其中部分差异蛋白质.结果 NS-398与顺铂联合组表达量下调的差异蛋白点22个,表达量上调蛋白点2个.选择其中17个表达量下调蛋白点、2个表达量上调蛋白点进行质谱鉴定,初步鉴定了NS-398与顺铂联合组6个表达下调的差异蛋白质,其中部分为细胞骨架蛋白,部分为与细胞增殖和凋亡相关的蛋白,部分为细胞代谢途径相关酶.结论 热休克蛋白90和磷酸丙糖异构酶可能参与了NS-398和顺铂对肺腺癌细胞增殖的协同抑制作用.

Different proteome of human lung adenocarcinoma cells treated with NS-398 and cisplatin

Background and objective Recent studies have shown that NS-398, a highly selective COX-2 inhibitor, can enhance the inhibition effects of cisplatin on adenocarcinoma cell proliferation, but the mechanism is still unknown. The aim of this study is to explore the mechanism about the synergistic effects of NS-398 and cisplatin to human lung adenocarcinoma cell line. Methods Differentially expressed proteins were separated in human lung adenocarcinoma cells treated with NS-398 and/or cisplatin by immobilized pH gradient-based two-dimensional gel electrophoresis (2-DE), then 19 out of obtained proteins were identified by peptide mass fingerprint (PMF) based on matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) and database searching. Results There were 22 down-regulated proteins and 2 up-regulated proteins in NS-398+cisplatin combination group compared with control groups. Finally six proteins were identified, in which some were cytokeratins, some were associated with proliferation and apoptosis, and the others were involved in metabolism of tumor cells. Conclusion The down-regulation of HSP90 and triosephosphate isomerase may be related to the synergistic effects of NS-398 and cisplatin on human lung adenocarcinoma cells.