选择性环氧合酶2抑制剂塞来昔布抑制B细胞淋巴瘤细胞株.docVIP

选择性环氧合酶-2抑制剂塞来昔布抑制B细胞淋巴瘤细胞株MDR-1 mRNA及Bcl-2 mRNA表达并增强表柔比星的抗肿瘤作用 化范例1，王玲燕2，赵鑫1，李莹1，邬扬炯1，高松1 1.复旦大学附属金山医院血液内科上海 201508； 2.复旦大学附属中山医院实验研究中心，上海 200032 [摘要]目的non-Hodgkin’s lymphoma, NHL)具有高表达环氧合酶-2(cyclooxygenase-2COX-2)的特征，而后者与P-糖蛋白及Bcl-2表达相关，可能导致NHL对化疗耐药。本研究目的即为探讨B细胞淋巴瘤细胞株中COX-2的表达以及选择性COX-2抑制剂塞来昔布增强淋巴瘤细胞对表柔比星抗肿瘤效应的敏感性及其可能机制。方法: 荧光定量PCR(qRT-PCR)及Western blot)方法分别检测Raji、Jeko-1和Namalwa等淋巴瘤细胞株以及正常人外周血B细胞的COX-2表达；以梯度浓度的塞来昔布作用于淋巴瘤细胞株，CCK-8方法检测细胞增殖的抑制程度，qRT-PCR检测各细胞株MDR-1及Bcl-2 mRNA表达的变化；表柔比星单独或联合不同浓度的塞来昔布处理Raji细胞株72后，CCK-8方法分析塞来昔布对表柔比星的增敏作用。结果: 各淋巴瘤细胞株及正常对照外周血B细胞均不表达COX-2。塞来昔布单药即可对各淋巴瘤细胞株产生程度不同的抗增殖效应；随着塞来昔布作用浓度的增加，除Jeko-1细胞不表达MDR-1外，其余细胞株MDR-1及Bcl-2 mRNA表达水平逐渐下降；塞来昔布明显增强表柔比星对Raji细胞的抗肿瘤活性，二者之间具有协同作用。结论: 选择性COX-2抑制剂塞来昔布下调B细胞淋巴瘤细胞株的MDR-1及Bcl-2 mRNA水平，并且增强表柔比星对淋巴瘤细胞的抗肿瘤效应。 [关键词] 环氧合酶-2；塞来昔布；淋巴瘤；MDR-1；Bcl-2DOI: 10.3969/j.issn.1007-3969.2015.06.0XX 中图分类号：R737.9　　文献标志码：A　　文章编号：1007-3639(2015)0-0XXX-0X 基金项目：上海市自然科学基金(13ZR1405700) 通作者：高松，E-mail：jsyyxyk2014@163.com Selective cyclooxygenase-2 inhibitor celecoxib sensitizes B-cell-originated lymphoma cell lines to epirubicin via down-regulation of MDR-1 mRNA and Bcl-2 mRNA expression HUA Fanli1, WANG Lingyan2, ZHAO Xin1, LI Ying1, WU Yangjiong1, GAO Song1 (1. Department of Hematology, Jinshan Hospital, Fudan University, Shanghai 201508, China; 2. Biomedical Research Centre, Zhongshan Hospital, Fudan University, Shanghai 200032, China) Correspondence to: GAO Song, E-mail: jsyyxyk2014@163.com [Abstract] Background and purpose: It has been demonstrated that cyclooxygenase-2 (COX-2) is over-expressed in some subtypes of non-Hodgkin’s lymphoma (NHL), and COX-2 correlates with the expression of P-glycoprotein and Bcl-2, which may contribute to chemotherapy-resistance in NHL. The purpose of this study was to investigate the expression of COX-2 in B-cell lymphoma cell lines and the potential mechanisms of celecoxib, a selective COX-2 inhibitor, to sensitize lymphoma cell lines to epirubicin. Methods: Quantitative fluorescent real-time poly