人源抗EB病毒潜伏膜蛋白1抗体Fab联合丝裂霉素C对鼻咽癌裸鼠移植瘤生长的抑制作用
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江苏省科技厅社会发展支撑计划项目(BE2009152);江苏省自然科学基金(BK2008481);南京医科大学科技发展基金重点项目(2005NYDZD13)


Anticancer effects of combination of anti-EBV-LMP1 humanized antibody Fab and mitomycin C on nasopharyngeal carcinoma xenografts in nude mice
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    摘要:

    目的: 观察联合应用人源抗EB病毒鼻咽癌潜伏膜蛋白1(latent membrane protein 1,LMP1)抗体Fab片段与丝裂霉素C(mitomycin C,MMC)对LMP1阳性鼻咽癌裸鼠移植瘤生长的抑制作用-方法:建立LMP1阳性鼻咽癌裸鼠移植瘤模型,20只成瘤裸鼠随机分成4组,即Fab组-MMC组-Fab+MMC组和对照组-腹腔注射药物, 每3天1次, 共5次-观察肿瘤生长-测量肿瘤体积,计算抑瘤率-免疫组化法检测肿瘤组织血管内皮生长因子(vascular endothelial growth factor,VEGF)表达-流式细胞术检测肿瘤细胞凋亡情况-结果:Fab组-MMC组和Fab+MMC组抑瘤率分别为18.90%-28.95%-49.12%-Fab组-Fab+MMC组VEGF表达量明显低于对照组(P < 0.05)-MMC组VEGF表达量和对照组相比,无统计学意义(P > 0.05)-MMC组-Fab+MMC组肿瘤细胞凋亡率分别为(11.84±1.50)%-(17.55±3.21)%,与对照组凋亡率(3.90±0.55)%相比,有显著差异(P < 0.01);Fab组凋亡率为(7.34±2.68)%,与对照组相比,无显著差异(P > 0.05)-结论:Fab及MMC均有抑瘤作用,联合使用效果优于单独使用,二者抑制肿瘤的作用途径不完全相同-Fab可能与抑制肿瘤血管生成有关,MMC可能与诱导肿瘤细胞凋亡增加有关-

    Abstract:

    Objective: To investigate the inhibitory activity of anti-latent membrane protein 1(LMP1)antibody fragment (Fab) combined with mitomycin C(MMC) on nasopharyngeal carcinoma NPC-LMP1 xenografts in nude mice. Methods:Nasopharyngeal carcinoma LMP1 cells (5×106) were subcutaneously transplanted in to 20 nude mice, which were randomly divided into Fab group, MMC group, Fab+MMC group and control group. The mice were injected once every 3 days. After corresponding treatments for 5 times, the tumor inhibition rate was evaluated, vascular endothelial growth factor (VEGF) was measured with immunohistochemistry, and the apoptotic rates were analyzed by flow cytometry. Results:The tumor growth inhibition rates in Fab group, MMC group, Fab+MMC group were 18.90%,28.95% and 49.12%,respectively. VEGF in Fab group and Fab+MMC group significantly reduced and showed lower expression compared with control group (P < 0.05). The apoptotic rates in MMC group and Fab+MMC group were (11.84±1.50)% and (17.55±3.21)%, dramatically decreased compared with control group(P < 0.01). Conclusion:Fab and MMC can both inhibit the subcutaneous xenograft tumor growth of NPC LMP1 cells in nude mice with distinct mechanisms. Fab may inhibit the angiogenesis of tumors, while MMC presumably induces apoptosis of tumor cells.

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毛 圆,张大为,陈仁杰,朱 进,冯振卿.人源抗EB病毒潜伏膜蛋白1抗体Fab联合丝裂霉素C对鼻咽癌裸鼠移植瘤生长的抑制作用[J].南京医科大学学报(自然科学版),2011,(2):156-160

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  • 收稿日期:2010-09-02
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