【摘要】 目的:探讨新设计CpG寡聚脱氧核苷酸(ODN)在小鼠体内的抗肿瘤作用及其对荷瘤小鼠免疫功能的影响。方法:建立C57BL/6小鼠腹腔、皮下荷黑素瘤肿瘤模型,腹腔注射CpGODN,观察荷瘤鼠生存时间、肿瘤生长曲线,计算抑瘤率。用酶联免疫吸附试验(ELISA)检测小鼠血清中白细胞介素(IL)12和免疫球蛋白E(IgE)含量;3H-TDR掺入法检测脾脏B细胞、T细胞增殖活性;51Cr释放法检测NK细胞杀伤活性;中性红法检测腹腔巨噬细胞吞噬功能。结果:CpG10,CpG11能明显延长腹腔接种肿瘤小鼠的生存时间,与阳性对照CPG1826相比P<0.01;二者平均抑瘤率(皮下荷瘤鼠)分别为(55.2±2.3)%与(40.7±1.7)%,显著高于CpG1826[抑瘤率(17.8±7.6)%](P<0.05,P<0.01)。CpG10/CpG11可促使荷瘤小鼠血清IL-12含量显著升高(P<0.01),IgE含量显著下降(P<0.01);明显刺激B细胞、T细胞增殖能力以及NK细胞的杀伤活性(P<0.01),对腹腔巨噬细胞的吞噬功能有显著提高(P<0.01)。CpGl0免疫增强活性较CPGl826更强(P<0.05)。结论:CpGODN能激活荷瘤鼠抗肿瘤免疫反应,从而抑制小鼠黑素瘤的生长,新结构寡核苷酸的CpG10呈现优于阳性对照的良好抗肿瘤免疫效应。更多还原

【Abstract】 Objective:To investigate the therapeutic and immunologic effects of novel CpG oligodeoxynucleotides on mu rine melanoma. Methods: Melanoma models were established by peritumoral or subcutaneous inoculation of B16 melanoma into C57BL/6 mice. Survival time was observed, and tumor size was measured regularly after peritumoral injection of PBS, CpG1826, CpG10, and CpG11. Serum levels of interleukin (IL) -12 and IgE were measured by enzyme-linked immunosor-bent assay. Proliferation of mouse B cells and T cells was determined by [3H] thymidine incorporation assay. The NK cy-totoxicity of splenocyte was detected with 4-h 51 Cr-release assay. The phagocytic ability of peritoneal macrophage was examined with neutral red chromometry. Results: All CpG ODNs could significantly prolong survival time of mice with B16 melanoma as compared with the PBS treatment (P<0. 01) , especially the CpG-10 group (P<0. 01). In addition, both CpG10 and CpG11 groups showed more effective as compared wtih CpG 1826 (P<0. 01). CpG ODN1826 inhibited the tumor growth by 17.8 % ,while CpG10 and CpG11 were 55.2 % and 40.7 % on day 20, respectively. In tumor-bearing mice, proliferation of B cells and T cells, NK cytotoxicity of splenocytes and phagocytic ability of peritoneal macrophage were lower than in normal mice (P < 0. 05). Above immune activities in CpG ODN-treated tumor-bearing mice dramatically increased compared with the PBS-treated ones (P<0.01) , and their increase in CpGlO group was more significant than in CpG1826 group (P<0.05). Conclusion:The present study suggests that CpG ODN activates the host anti-tumor immune response to inhibit the growth of melanoma in mice. The novel CpG10 presents potent activity.更多还原