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目的观察白细胞介素4(IL-4)局部过继免疫治疗小鼠膀胱癌的效应并探讨其相关机制。方法利用4~5周龄近交系T739小鼠建立皮下移植性膀胱移行细胞癌模型并随机分为对照组及IL-4组。于癌细胞接种后5天、10天、15天.瘤体内浸润注射0.1mlIL-4(100U/ml)或Hanks平衡盐溶液(对照组)。定期测量肿瘤体积,MTT比色法检测荷瘤鼠细胞免疫功能.观察膀胱癌组织病理学改变及荷瘤鼠生存期。结果局部免疫治疗2周后.比较对照组,IL-4明显抑制了膀胱癌体积的增长(P<0.05),IL-4组脾脏NK细胞活性(39.48%±4.85%)及T淋转刺激指数(1.30±0.04)较对照组NK细胞活性(25.28%±4.62%)及T淋转刺激指数(1.03±0.13)显著提高(P均<0.05)。对照组及IL-4组荷瘤鼠平均生存期分别为21.56±3.47天及28.44±5.08天,两者有显著性差异(P<0.01)。IL-4组肿瘤间质内可见大量淋巴细胞浸润,癌组织形成片状坏死灶。结论外源性IL-4局部应用,通过趋化、激活淋巴细胞等,诱导细胞免疫反应.直接发挥较强的抗膀胱癌效应.也有助于机体全身抗瘤免疫功能的恢复。
Objective To investigate the effect of local adoptive immunotherapy with interleukin-4 (IL-4) on bladder cancer in mice and to explore its mechanism. Methods T739 mice of 4 ~ 5 weeks old inbred line were used to establish subcutaneous transplanted bladder transitional cell carcinoma model and divided randomly into control group and IL-4 group. 5 days, 10 days, 15 days after inoculation of cancer cells. Tumor infiltration was injected with 0.1 ml of IL-4 (100 U / ml) or Hanks balanced salt solution (control group). The tumor volume was measured regularly, and the cellular immune function was detected by MTT colorimetry. Observe the pathological changes of bladder cancer and tumor-bearing mice survival. Results Local immunotherapy after 2 weeks. Compared with the control group, IL-4 significantly inhibited the growth of bladder cancer (P <0.05), the activity of NK cells (39.48% ± 4.85%) and T lymphocyte stimulation index .30 ± 0.04) were significantly higher than those in the control group (25.28% ± 4.62%) and T lymphocyte stimulation index (1.03 ± 0.13) (all P <0.05). The average survival time in control group and IL-4 group was 21.56 ± 3.47 days and 28.44 ± 5.08 days, respectively, with significant difference (P <0.01). IL-4 group showed a large number of tumor stroma infiltration of lymphocytes, cancerous tissue to form flaky necrosis. Conclusion Topical application of exogenous IL-4 induces cellular immune responses by chemotaxis and activation of lymphocytes. Directly play a strong anti-bladder cancer effect. Also contribute to the body’s systemic anti-tumor immune function recovery.