CAJ | 학술논문

目的：观察表观遗传修饰的肿瘤细胞疫苗皮下注射后对仓鼠胰腺癌皮下移植瘤的抗肿瘤效应。方法通过皮下注射N-亚硝基双-2-氧丙基建立仓鼠胰腺癌模型,将仓鼠胰腺肿瘤取出、切碎,取0.5 cm ×0.5 cm ×0.5 cm的肿瘤组织移植在健康仓鼠的腹股沟皮下,建立仓鼠皮下移植瘤模型。采用组蛋白去乙酰化酶抑制剂和甲基化转移酶抑制剂表观遗传修饰胰腺癌PANC-1细胞,构建肿瘤细胞疫苗,同时构建对照细胞疫苗。将12只荷移植瘤仓鼠随机分为疫苗注射组和对照组(各6只),疫苗注射组皮下注射肿瘤细胞疫苗,对照组皮下注射对照细胞疫苗。荷移植瘤仓鼠于第4周统一处死,观察两组肿瘤生长情况及瘤组织中环氧合酶2(COX-2)、5脂氧合酶(5-LOX)、半乳凝素1(GAL-1)、半乳凝素3(GAL-3)、主要组织相容性复合体(MHC)Ⅰ、MHC Ⅱ的表达变化。结果疫苗注射组移植瘤大小随时间延长呈递减趋势,对照组移植瘤大小随时间延长呈递增趋势；疫苗治疗组肿瘤大小平均为0.39 cm、对照组为0.82 cm,两组相比,P<0.05；疫苗注射组移植瘤组织中COX-2、5-LOX、GAL-1、GAL-3的表达较对照组降低,而MHCⅠ、MHCⅡ表达较对照组升高,两组相比,P均<0.01。结论表观遗传修饰的肿瘤细胞疫苗皮下注射能有效延缓仓鼠胰腺癌移植瘤的生长,降低移植瘤组织中 COX-2、5-LOX、GAL-1、GAL-3的表达,上调MHC Ⅰ、MHC Ⅱ的表达。
목적：관찰표관유전수식적종류세포역묘피하주사후대창서이선암피하이식류적항종류효응。방법통과피하주사N-아초기쌍-2-양병기건립창서이선암모형,장창서이선종류취출、절쇄,취0.5 cm ×0.5 cm ×0.5 cm적종류조직이식재건강창서적복고구피하,건립창서피하이식류모형。채용조단백거을선화매억제제화갑기화전이매억제제표관유전수식이선암PANC-1세포,구건종류세포역묘,동시구건대조세포역묘。장12지하이식류창서수궤분위역묘주사조화대조조(각6지),역묘주사조피하주사종류세포역묘,대조조피하주사대조세포역묘。하이식류창서우제4주통일처사,관찰량조종류생장정황급류조직중배양합매2(COX-2)、5지양합매(5-LOX)、반유응소1(GAL-1)、반유응소3(GAL-3)、주요조직상용성복합체(MHC)Ⅰ、MHC Ⅱ적표체변화。결과역묘주사조이식류대소수시간연장정체감추세,대조조이식류대소수시간연장정체증추세；역묘치료조종류대소평균위0.39 cm、대조조위0.82 cm,량조상비,P<0.05；역묘주사조이식류조직중COX-2、5-LOX、GAL-1、GAL-3적표체교대조조강저,이MHCⅠ、MHCⅡ표체교대조조승고,량조상비,P균<0.01。결론표관유전수식적종류세포역묘피하주사능유효연완창서이선암이식류적생장,강저이식류조직중 COX-2、5-LOX、GAL-1、GAL-3적표체,상조MHC Ⅰ、MHC Ⅱ적표체。
Objective To observe the anti-tumor effects of tumor cell vaccine by epigenetic modification on pancreatic cancer of hamster through subcutaneous injection. Methods The hamster pancreatic cancer models were set up by subcu-taneous injection of N-nitrosobis-2-oxopropylamin. We removed the pancreatic tumor, chopped, and took 0. 5 cm × 0. 5 cm × 0. 5 cm tumor tissue to transplant into groin skin of healthy hamsters, and then the hamster subcutaneous transplanted tumor models were set up. In addition, PANC-1 cells were treated by histone deacetylase inhibitors and methyl transferase inhibitor epigenetic modification to make the tumor cell vaccine. Meanwhile, the control cell vaccine was set up. Twelve hamster pancreatic cancer xenografts were divided into two groups, 6 in each group: the vaccinated group and the control group which were respectively treated with tumor cell vaccine and control cell vaccine by subcutaneous injection. The tumor growth and the expression of cyclooxyg enase-2 (COX-2), 5-LOX, GAL-1, GAL-3, MHC Ⅰ and MHC Ⅱ of the two groups were observed. Results In the vaccinated group, the tumor size ( mean size 0. 39 cm) was decreased with the prolonged time, but in the control group, the tumor size ( mean size 0. 82 cm) was increased with the prolonged time. Tumor size was statistical different between the two groups (P<0. 05). The expression of COX-2, 5-LOX, GAL-1 and GAL-3 was lower in the vaccinated group as compared with that of the control group, and MHCⅠ, MHCⅡexpression was higher than that of the control group, the difference was statistically significant (all P<0. 01). Conclusion The epige-netic modification tumor vaccine can effectively delay the growth of transplanted tumor, reduce the expression of COX-2, 5-LOX, GAL-1 and GAL-3, and up-regulate the expression of MHC Ⅰ and MHC Ⅱ.