Department of Microbiology and Immunology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
Exp Mol Pathol. 2010 Jun;88(3):371-5. doi: 10.1016/j.yexmp.2010.02.001. Epub 2010 Feb 18.
Although current treatments based on the use of B-cell-specific anti-CD20 monoclonal antibodies and aggressive combinatorial chemotherapy have improved the survival of patients suffering from B-cell non-Hodgkin's lymphoma (NHL), some individuals fail to respond to treatment and relapses remain common. New and more effective treatments for B-cell NHL are therefore required. Bovine lactoferricin (LfcinB) is a cationic antimicrobial peptide that is cytotoxic for several human tumor cell lines but does not harm healthy cells. Here we show that in vitro treatment with LfcinB caused Raji and Ramos human B-lymphoma cells to die by apoptosis, as indicated by DNA fragmentation, chromatin condensation, and nuclear disintegration. LfcinB killed B-lymphoma cells more efficiently at low serum concentrations and was inhibited in the presence of exogenous bovine serum albumin, suggesting partial neutralization of cationic LfcinB by anionic serum components. LfcinB-induced apoptosis in B-lymphoma cells was caspase-independent since caspase-3 activation was not detected by Western blotting and the general caspase inhibitor z-VAD-fmk did not prevent LfcinB-induced DNA fragmentation. Importantly, immune-deficient SCID/beige mice that were inoculated intravenously with Ramos B-lymphoma cells in order to model B-cell NHL exhibited extended survival following systemic administration of LfcinB, indicating that LfcinB warrants further investigation as a novel therapeutic agent for the possible treatment of B-cell NHL.
尽管基于使用 B 细胞特异性抗 CD20 单克隆抗体和强化联合化疗的当前治疗方法已经改善了患有 B 细胞非霍奇金淋巴瘤（NHL）的患者的生存，但一些患者对治疗没有反应，复发仍然很常见。因此，需要新的、更有效的 B 细胞 NHL 治疗方法。牛乳铁蛋白（LfcinB）是一种阳离子抗菌肽，对几种人类肿瘤细胞系具有细胞毒性，但不会伤害健康细胞。在这里，我们表明在体外用 LfcinB 处理会导致 Raji 和 Ramos 人 B 淋巴细胞瘤细胞通过细胞凋亡而死亡，如 DNA 片段化、染色质浓缩和核解体所表明的那样。LfcinB 在低血清浓度下更有效地杀死 B 淋巴细胞瘤细胞，并且在外源牛血清白蛋白存在下被抑制，这表明阴离子血清成分部分中和了阳离子 LfcinB。LfcinB 诱导的 B 淋巴细胞瘤细胞凋亡与 Caspase 无关，因为 Western blot 未检测到 Caspase-3 的激活，并且一般 Caspase 抑制剂 z-VAD-fmk 不能阻止 LfcinB 诱导的 DNA 片段化。重要的是，免疫缺陷的 SCID/beige 小鼠静脉内接种 Ramos B 淋巴细胞瘤细胞以模拟 B 细胞 NHL，在全身给予 LfcinB 后表现出延长的存活期，表明 LfcinB 值得进一步研究，作为一种新的治疗剂，可能用于治疗 B 细胞 NHL。
