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目的探讨白介素-18(IL-18)影响肝癌裸鼠皮下移植瘤浸润的T细胞子集变化的机制。方法以HepG2细胞在裸鼠皮下接种,形成人肝癌皮下移植瘤的同时,以不同剂量IL-18分为4组治疗,4组分别腹腔注射IL-18 0.75,1.00,1.25,0(模型组)μg(0.1 mL)/只,治疗4周,另设正常对照组。观察肿瘤的生长速度和瘤体大小的变化。4周后处死取肿瘤组织和脾组织,免疫磁珠阴选组织中CD4+T细胞,流式细胞术检测各组肿瘤组织及脾组织中IL-17+/IFN-γ-CD4+T(Th17细胞)、IL-17-/IFN-γ+CD4+T(Th1)和IL-17+/IFN-γ+CD4+T细胞的变化。结果 HepG2细胞株建立了裸鼠肝癌皮下移植瘤模型,IL-18抑制人肝癌皮下移植瘤的形成及转移,治疗时间越长剂量越大,抑制效果越明显;与正常对照组比较,肿瘤组织中Th17和IL-17+/IFN-γ+CD4+T细胞浸润数目增加,Th1细胞降低,与脾组织中一致,与正常对照组比较有显著差异(P<0.05)。给IL-18后,随着剂量的增加,Th1细胞增加,IL-17+/IFN-γ+CD4+T细胞和Th17细胞浸润数目降低,给药组与模型组比较有显著差异(P<0.05或0.01)。结论 IL-17+/IFN-γ+CD4+T细胞数目在裸鼠移植瘤及其脾组织中增加,可能是在肿瘤环境中,促进其向Th17细胞分化;IL-18通过诱导IFN-γ的生成促进Th1细胞的生成,呈正反馈效应抑制肿瘤的增殖和转移。
Objective To investigate the mechanism of interleukin-18 (IL-18) affecting the subsets of T cells infiltrating subcutaneously implanted tumor in nude mice. Methods HepG2 cells were subcutaneously inoculated into nude mice to form human hepatocellular carcinoma xenografts. At the same time, HepG2 cells were divided into 4 groups with different dosages of IL-18, and 4 groups were intraperitoneally injected with IL-18 0.75,1.00,1.25,0 (model group) μg (0.1 mL) / only for 4 weeks, another normal control group. Observation of tumor growth rate and tumor size changes. After 4 weeks, the tumor tissues and spleen tissues were harvested, and the CD4 + T cells in the negative selection beads were immunoprecipitated. The levels of IL-17 + / IFN-γ-CD4 + T in the tumor tissues and spleen tissues were measured by flow cytometry IL-17- / IFN-γ + CD4 + T (Th1) and IL-17 + / IFN-γ + CD4 + T cells. Results HepG2 cell line established a subcutaneous xenograft model of human hepatocellular carcinoma in nude mice. IL-18 inhibited the formation and metastasis of subcutaneous xenografts in human hepatocellular carcinoma. The longer the treatment time, the greater the dose and the more obvious the inhibitory effect. Compared with the normal control group, The number of Th17 and IL-17 + / IFN-γ + CD4 + T cells increased, while Th1 cells decreased, which was consistent with that in spleen. There was a significant difference between the two groups (P <0.05). After IL-18 was administered, the number of Th1 cells increased and the number of infiltrated IL-17 + / IFN-γ + CD4 + T cells and Th17 cells decreased as the dose increased. There was a significant difference between the treated group and the model group (P <0.05 Or 0.01). Conclusion The number of IL-17 + / IFN-γ + CD4 + T cells in nude mice xenografts and their splenic tissues increased, which may be in the tumor environment to promote Th17 cell differentiation; IL-18 through the induction of IFN-γ Generated to promote the formation of Th1 cells, a positive feedback inhibition of tumor proliferation and metastasis.