MB49 Murine Urothelial Carcinoma: Molecular and Phenotypic Comparison to Human Cell Lines as a Model of the Direct Tumor Response to Bacillus Calmette-Guerin
MB49 Murine Urothelial Carcinoma: Molecular and Phenotypic Comparison to Human Cell Lines as a Model of the Direct Tumor Response to Bacillus Calmette-Guerin
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DOI：
10.1016/j.juro.2009.08.018
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发表时间：
2009-12-01
影响因子：
6.6
通讯作者：
See, William A.
中科院分区：
文献类型：
--
作者：
Chen, Fanghong;Zhang, Guangjian;See, William A.
目的：小鼠尿路上皮癌细胞系MB49是一种广泛应用的体内外尿路上皮癌模型。关于该细胞系相对于人类细胞系的分子和表型反应方面的比较数据很少。我们比较了卡介苗对人尿路上皮癌细胞系T24(ATCC(R))和253J细胞的作用。材料和方法：卡介苗作用6h后，MB49细胞的分子终点是信号通路激活(核因子-kappa B、AP1和C/EBP)、基因表达(IL-6和p21)、HMGB1释放/反应性和基因表达谱。结果：卡介苗刺激MB49细胞后，核因子-kappa B、AP1、C/EBP、IL-6和p21报告结构均被激活。基因表达谱显示炎症/免疫聚集反应。卡介苗降低细胞存活率并诱导细胞周期停滞于G1期。卡介苗处理MB49细胞可诱导caspase非依赖性细胞死亡，同时降低对促凋亡剂的敏感性。细胞死亡与坏死细胞死亡标记物HMGB1的释放有关。结论：MB49细胞对卡介苗的分子和表型反应与人尿路上皮癌细胞系相同。MB49细胞似乎是研究卡介苗作为抗尿路上皮癌药物的一个很好的模型。
Purpose: The mouse urothelial carcinoma cell line MB49 is widely used as an in vitro and in vivo model of urothelial carcinoma. Little comparative data exist on the molecular and phenotypic responses of this cell line relative to human cell lines. We compared the effect of bacillus Calmette-Guerin on the MB49 cell line relative to responses previously observed in the human urothelial carcinoma lines T24 (ATCC (R)) and 253J.Materials and Methods: Molecular end points in MB49 cells after bacillus Calmette-Guerin exposure were signaling pathway activation (NF-kappa B, AP1 and C/EBP), gene expression (IL-6 and p21), HMGB1 release/responsiveness and gene expression profiling at 6 hours. Phenotypic response end points were direct cytotoxicity using dye exclusion, viability on MTT assay, apoptotic sensitivity and cell cycle compartmentalization.Results: NF-kappa B, AP1, C/EBP, IL-6 and p21 reporter constructs were activated in MB49 cells in response to bacillus Calmette-Guerin. Gene expression profiles showed an inflammatory/immune clustering response. Bacillus Calmette-Guerin decreased cell viability and induced G1 cell cycle arrest. Treatment of MB49 cells with bacillus Calmette-Guerin induced caspase independent cell death while simultaneously decreasing sensitivity to pro-apoptotic agents. Cell death was associated with release of the necrotic cell death marker HMGB1. MB49 cells expressed HMGB1 receptors and activated intracellular NF-kappa B signaling pathways in response to bacillus Calmette-Guerin.Conclusions: MB49 cells show molecular and phenotypic responses to bacillus Calmette-Guerin that replicate those observed in human urothelial carcinoma lines. MB49 cells appear to be an excellent model in which to study bacillus Calmette-Guerin as an antitumor agent for urothelial carcinoma.