重组IL-2联合大蒜素治疗胰腺癌的作用机制  

Mechanism of action of recombinant interleukin-2 combined with allicin in treatment of pancreatic cancer

作　　者：朱立宁[1] 林峰[1] 商振宁[1] 李惠[1] 肖轶群[1] 袁秋霞[1] 

机构地区：[1]四平市中心人民医院消化内科,吉林四平136000

出　　处：《临床肝胆病杂志》2016年第10期1943-1946,共4页Journal of Clinical Hepatology

基　　金：吉林省卫生厅自筹项目(2013zc026)

摘　　要：目的评价重组白细胞介素(r IL-2)联合大蒜素(allicin)治疗胰腺癌的效果并探讨其相关机制。方法构建裸鼠肿瘤异位移植模型,60只裸鼠随机分为对照组、r IL-2治疗组、allicin治疗组及联合治疗组。治疗后4周,分离获得外周血,记录肿瘤的体积、质量和生存时间并计算生存率。流式细胞术分析肿瘤细胞凋亡情况,同时检测CD4+、CD8+T淋巴细胞和自然杀伤细胞(NK细胞);使用ELISA法检测IFNγ的水平。Western Blot分析肿瘤组织蛋白Bcl-2的表达水平。计量资料组间比较采用方差分析,进一步两两比较采用SNK-q检验。结果治疗后4周发现,r IL-2组、allicin组及联合治疗组肿瘤体积与对照组比较均明显降低,且差异均有统计学意义(P值均<0.05),其中联合治疗组降低最为显著(P<0.01),其肿瘤抑制率为90.5%。联合治疗能够显著延长小鼠的生存时间(联合治疗组在55 d时仍有60%的小鼠存活)。联合治疗组的肿瘤细胞凋亡率与对照组比较显著升高[(23.3±4.3)%vs(9.0±3.7)%],差异有统计学意义(P<0.05),联合治疗组中促凋亡蛋白Bcl-2的表达水平与对照组比较明显增加。治疗组外周血中CD4+、CD8+T淋巴细胞及NK细胞的比例相比于对照组有显著升高(F值分别为23.74、26.38、19.72,P值均<0.001)。与其他组比较,联合治疗组IFNγ的水平显著升高(F=9.84,P=0.026)。结论 r IL-2和allicin联合治疗能够通过增强固有免疫和适应性免疫的效应来改善胰腺癌患者的生存状况。Objective To investigate the effect of recombinant interleukin-2（ r IL-2） combined with allicin in the treatment of pancreatic cancer and related mechanisms. Methods A nude mouse xenograft model was established. A total of 60 nude mice were randomized into control group,r IL-2 treatment group,allicin treatment group,and combined treatment group. At 4 weeks after treatment,peripheral blood was collected,tumor volume,tumor weight,and survival time were recorded,and survival rates were calculated. Flow cytometry was used to analyze the apoptosis of tumor cells and measure the percentages of CD4＋T,CD8＋T,and natural killer（ NK） cells,ELISA was used to measure the level of interferonγ（ IFNγ）,and Western blot was used to measure the expression of Bcl-2 protein in tumor tissue. An analysis of variance was used for comparison of continuous data between groups,and SNK-q test was used for further comparison between any two groups. Results At 4 weeks after treatment,the r IL-2 treatment group,allicin treatment group,and combined treatment group showed significant reductions in tumor volume compared with the control group（ all P〈0. 05）,and the combined treatment group showed the greatest reduction（ P〈0. 01）. The combined treatment group had a tumor inhibition rate of 90. 5% and a prolonged survival time（ 60% of the mice survived at 55 days）. Compared with the control group,the combined treatment group showed significant increases in the apoptosis rate of tumor cells（ 23. 3% ± 4. 3% vs 9. 0% ± 3. 7%,P〈0. 05） and the expression of pro-apoptotic protein Bcl-2. The treatment groups showed significant increases in the percentages of CD4＋T,CD8＋T,and NK cells compared with the control group（ F = 23. 74,26. 38,and 19. 72,all P〈0. 001）. Compared with the other three groups,the combined treatment group showed a significant increase in the IFNγlevel（ F = 9. 84,P = 0. 026）. Conclusion Combined treatment with allicin and r IL-2 can enhance the innate immunity and adaptive immunity a

关 键 词：胰腺肿瘤 白细胞介素2 大蒜辣素 T淋巴细胞 干扰素γ 重组 

分 类 号：R735.9[医药卫生—肿瘤] R392.12[医药卫生—临床医学]