免疫刺激DNA（CpG-寡脱氧核苷酸）在小鼠C57-BL6/MB-49移行细胞癌模型中的抗肿瘤作用。

Antineoplastic effect of immunostimulatory DNA (CpG-ODN) in a murine C57-BL6/MB-49 transitional cell carcinoma model.

作者信息

Hegele Axel, Dalpke Alexander, Barth Peter, Varga Zoltan, Heeg Klaus, Hofmann Rainer, Olbert Peter

机构信息

Department of Urology and Pediatric Urology, Philipps University, Marburg, Germany.

出版信息

Anticancer Res. 2004 Jul-Aug;24(4):2225-30.

PMID:15330165

Abstract

BACKGROUND

Intravesical BCG installation is the standard of care in the prophylaxis of recurrent intermediate and high-risk transitional cell carcinoma (TCC), but its mode of action has not yet been elucidated. However, a Th-1 biased immune response is postulated Cell culture and animal models demonstrated the efficacy of synthetic CpG-oligodeoxynucleotides (ODN) as inducer and adjuvant for a strong Th1-response. The purpose of our study was to evaluate the antineoplastic effect of locally administered CpG ODN in a subcutaneous murine bladder cancer model.

MATERIALS AND METHODS

A subcutaneous murine TCC model was established in female C57/BL6 mice using the corresponding syngeneic MB49 TCC cell line. Three groups of 5 animals received a cell suspension, standardized for 1x10(6) cells/50 microl, injected s.c. into the right and left flank. Group I received 10 nmol of CpG-ODN only into the right cell depot. Group II received 10 nmol of GpC ODN. Group III served as untreated control and received only PBS. The animals were examined at various time points after injection until sacrifice on day 14. Tumor or scar tissue were excised, weighed and examined histopathologically (HE-stain).

RESULTS

Tumor sizes and weights showed no side differences. The average tumor weight on day 14 was 171 mg (SD +/- 8.9), 110 mg (SD +/- 19.2) and 18 mg (SD +/- 6.1), respectively, in groups III, II and I (p<0.05). Histopathology revealed solid vital epithelial tumors in group III and reduced vital tumor mass with central necrosis and moderate mononuclear infiltration in group II. Group I showed almost complete tumor necrosis and a considerable mononuclear inflammatory response.

CONCLUSION

Immunostimulatory DNA has promising antineoplastic activity in a murine subcutaneous TCC-model. The histological findings suggest an immunologically-mediated mode of action. Further investigations are necessary to elucidate the immunological response.

摘要

背景

膀胱内灌注卡介苗是预防复发性中高危移行细胞癌（TCC）的标准治疗方法，但其作用机制尚未阐明。然而，推测其具有偏向Th-1的免疫反应。细胞培养和动物模型证明合成的CpG-寡脱氧核苷酸（ODN）作为诱导剂和佐剂可引发强烈的Th1反应。我们研究的目的是评估在皮下小鼠膀胱癌模型中局部给予CpG ODN的抗肿瘤作用。

材料与方法

使用相应的同基因MB49 TCC细胞系在雌性C57/BL6小鼠中建立皮下小鼠TCC模型。三组，每组5只动物，接受细胞悬液（标准化为1×10⁶个细胞/50微升），皮下注射到左右侧腹。第一组仅在右侧细胞接种部位给予10 nmol的CpG-ODN。第二组给予10 nmol的GpC ODN。第三组作为未治疗对照，仅接受PBS。在注射后的不同时间点对动物进行检查，直至第14天处死。切除肿瘤或瘢痕组织，称重并进行组织病理学检查（苏木精-伊红染色）。

结果

肿瘤大小和重量无显著差异。第14天时，第三组、第二组和第一组的平均肿瘤重量分别为171毫克（标准差±8.9）、110毫克（标准差±19.2）和18毫克（标准差±6.1）（p<0.05）。组织病理学显示，第三组为实性存活上皮肿瘤，第二组存活肿瘤质量减少，伴有中央坏死和中度单核细胞浸润。第一组显示几乎完全的肿瘤坏死和相当程度的单核细胞炎症反应。