Yao Qiang-Hua, Tang Yan-Jing, Gao Feng-Hou, Tang Jing-Yan
Department of Hematology/Oncology, Shanghai Children's Medical Center, The Third People's Hospital, Medical College of Shanghai Jiaotong University, Shanghai, 200127, PR China.
Ai Zheng. 2009 Apr;28(4):344-9.
Synthetic CpG oligodeoxynucleotides(CpG ODN) containing unmethylated CpG dinucleotide motifs, which mimic the effects of bacterial DNA, can stimulate the host's immune defense to reject cancer cells as "non-self" signal. This study was to evaluate the antitumor effect of CpG ODN against human neuroblastoma xenografts in nude mice depending on the innate immunity.
The cytotoxicity of CpG ODN on neuroblastoma SK-N-MC cells was detected by WST-1 assay in vitro. Neuroblastoma xenografts were built subcutaneously in nude mice. When palpable tumor developed, the mice were randomized into normal saline (NS), non-CpG ODN, and CpG ODN groups (each group contained six mice), and were administered every other day for two weeks. When tumor grew to 5 cm3, the mice were killed to observe tumor morphology by histology and histochemistry.
CpG ODN had no cytotoxicity on SK-N-MC cells in vitro. Tumor volume was significantly smaller in CpG ODN group than in NS and non-CpG ODN groups at the end of the observation [(0.14+/-0.03) cm3 vs. (2.97+/-0.40) cm3 and (3.80+/-1.12) cm3, P<0.01]. On HE-stained sections, the tumor tissues of CpG ODN group showed intratumoral infiltration of inflammatory cells and large areas of necrosis, whereas those of controls showed less infiltration and no necrosis. By immunohistochemistry, the tumor tissues of CpG ODN group showed more natural killer (NK) cells and macrophages as compared with those of control groups.
CpG ODN may have therapeutic effect on neuroblastoma in nude mice via mediating the activity of NK cells and macrophages.
合成的含未甲基化CpG二核苷酸基序的寡脱氧核苷酸（CpG ODN）可模拟细菌DNA的作用，作为“非自身”信号刺激宿主的免疫防御以排斥癌细胞。本研究旨在评估CpG ODN依赖先天免疫对裸鼠人神经母细胞瘤异种移植瘤的抗肿瘤作用。
采用WST-1法体外检测CpG ODN对神经母细胞瘤SK-N-MC细胞的细胞毒性。将神经母细胞瘤异种移植瘤皮下接种于裸鼠。当可触及肿瘤形成时，将小鼠随机分为生理盐水（NS）组、非CpG ODN组和CpG ODN组（每组6只小鼠），每隔一天给药，共两周。当肿瘤体积长至5 cm3时，处死小鼠，通过组织学和组织化学观察肿瘤形态。
CpG ODN体外对SK-N-MC细胞无细胞毒性。观察结束时，CpG ODN组肿瘤体积明显小于NS组和非CpG ODN组[（0.14±0.03）cm3 vs.（2.97±0.40）cm3和（3.80±1.12）cm3，P<0.01]。在苏木精-伊红（HE）染色切片上，CpG ODN组肿瘤组织显示瘤内炎性细胞浸润和大片坏死，而对照组浸润较少且无坏死。通过免疫组织化学检测，与对照组相比，CpG ODN组肿瘤组织显示更多的自然杀伤（NK）细胞和巨噬细胞。
CpG ODN可能通过介导NK细胞和巨噬细胞的活性对裸鼠神经母细胞瘤具有治疗作用。
