CpG-ODN治疗小鼠膀胱肿瘤的实验研究

Immunotherapeutic effects of CpG oligodeoxynucleotide on murine transitional cell carcinoma

目的探讨含CpG序列的寡脱氧核糖核苷酸(CpG Oligodeoxynucleotide,CpG-ODN)对小鼠膀胱肿瘤的治疗作用。方法建立BTT739荷瘤小鼠动物模型,随机分为CpG-ODN治疗组和PBS对照组,于肿瘤细胞接种后第7、14天给予治疗,每组分两亚组,分别用于测量瘤重、体积及用于观察荷瘤小鼠存活情况。ELISA法检测小鼠血清中IL-12水平。流式细胞仪检测肿瘤组织中浸润性树突状细胞表面共刺激分子CD80、CD86的表达。结果第2次治疗7d后,平均瘤重CpG-ODN组为(3.30±0.81)g,对照组为(4.50±0.47)g(P<0.01),平均体积CpG-ODN组为(3.57±0.84)cm3,对照组为(4.84±0.58)cm3(P<0.01),CpG-ODN组荷瘤小鼠生存期长于PBS对照组(P<0.05)。治疗组及对照组小鼠血清中IL-12浓度分别为(391.5±28.4)pg/mL和(257.2±13.7)pg/mL(P<0.01)。肿瘤组织中浸润性树突状细胞(Tumor infiltrating dendritic cell,TIDC)表面CD80、CD86表达水平治疗组分别为(17.75±3.13)%、(18.72±2.79)%,对照组分别为(11.32±1.18)%(P<0.01)、(12.65±1.22)%(P<0.01)。结论CpG-ODN对膀胱肿瘤荷瘤小鼠具有抑瘤效应和生存期延长作用,其机制主要是通过诱导DC成熟、促进Th1型细胞因子分泌、诱导免疫应答向Th1细胞分化。

Objective To investigate the immunotherapeutic effects of CpG oligodeoxynucleotide （CpG-ODN） on murine transitional cell carcinoma. Methods After the BTT739 bladder tumor model in 24 T739 mice was successfully established, CpG-ODN and phosphate buffered saline were injected respectively into the margins of the tumor （peritumoral） on day 7 and day 14 after tumor cells inoculation. Tumor weight, volume, and the life span of mice were recorded. IL-12 level in serum was assessed by ELISA. The expression levels of CD80 and CD86 on TIDC of tumor tissues were detected by flow cytometry. Results Seven days after the second injection, average tumor weight was （3.30±0.81） g and （4.50±0.47） g respectively in the CpG-ODN group and the control group （ P 〈 0.01）. Average tumor volume was （3.57±0.84） cm^3 and （4.84±0.58） cm^3 respectively in the CpG-ODN group and the control group （P〈0.01）. The life span of mice in the CpG-ODN group.was significantly longer than that in the control group （ P 〈 0.05）. The level of IL-12 was （391.5 ±28.4） pg/mL and （257.2 ± 13.7） pg/mL respectively in the CpG-ODN group and the control group （ P 〈 0.01）. The expression levels of CD80 on TIDC was 17.75% ±3.13% and 11.32% ± 1.18% respectively in the CpG-ODN treatment group and the control group （P〈0.01）. The expression level of CD86 on TIDC was 18.72% ± 2.79% and 12.65% ± 1.22% respectively in the CpG-ODN treatment group and the control group （ P 〈 0.01）. Conclusion CpG-ODN can inhibit tumor growth and prolong the hying time of T739 mice with BTT739 bladder tumor via inducing the maturation of DC and promoting the secretion of Thl cytokine IL-12 which polarize immune response to Thl ceils.