Department of Urology, Karolinska University Hospital, Stockholm, Sweden; Urology Laboratory, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Department of Urology, Karolinska University Hospital, Stockholm, Sweden; Urology Laboratory, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Laboratory Medicine, Division of Clinical Chemistry, Karolinska Institutet and Karolinska University Hospital Huddinge, Stockholm, Sweden; Stockholm University, Department of Genetics, Microbiology and Toxicology, Stockholm, Sweden.
Cancer Lett. 2014 Jun 28;348(1-2):119-25. doi: 10.1016/j.canlet.2014.03.014. Epub 2014 Mar 18.
The anti-tumour mechanisms following Bacillus Calmette-Guérin (BCG) treatment of bladder-cancer remain largely unknown. Previous studies have shown involvement of nitric-oxide (NO) formation in the BCG-mediated effect. We analyzed the effects of macrophage secreted factors (MSFs) from BCG-stimulated RAW264.7 cells on the bladder-cancer cell line MBT2. Direct treatment with BCG did not induce NO in MBT2-cells whereas supernatant from BCG-stimulated macrophages increased NOS2 mRNA and protein expression, NO concentrations and cell-death. Blocking NO-synthesis with the NOS-inhibitor L-NAME did not affect levels of cell-death suggesting cytotoxic pathways involving other signalling molecules than NO. Several such candidate genes were identified in a microarray.
BCG 治疗膀胱癌的抗肿瘤机制在很大程度上尚不清楚。先前的研究表明，一氧化氮（NO）的形成参与了 BCG 介导的作用。我们分析了来自 BCG 刺激的 RAW264.7 细胞的巨噬细胞分泌因子（MSFs）对膀胱癌细胞系 MBT2 的影响。BCG 直接处理不会诱导 MBT2 细胞中的 NO，而来自 BCG 刺激的巨噬细胞的上清液则增加了 NOS2 mRNA 和蛋白表达、NO 浓度和细胞死亡。用 NOS 抑制剂 L-NAME 阻断 NO 合成不会影响细胞死亡水平，这表明细胞毒性途径涉及比 NO 更复杂的信号分子。在基因芯片中鉴定了几个这样的候选基因。
