[Antitumor effect of CpG oligonucleotides on human neuroblastoma xenografts in nude mice].
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
CpG ODN may have therapeutic effect on neuroblastoma in nude mice via mediating the activity of NK cells and macrophages.
Yao
Qiang-Hua
QH
Department of Hematology/Oncology, Shanghai Children's Medical Center, The Third People's Hospital, Medical College of Shanghai Jiaotong University, Shanghai, 200127, PR China.
Tang
Yan-Jing
YJ
Gao
Feng-Hou
FH
Tang
Jing-Yan
JY
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D018899:CpG Islands; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000473:pathology*; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D011897:Random Allocation; D047368:Tumor Burden / Q000187:drug effects*; D023041:Xenograft Model Antitumor Assays
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides