化疗治愈荷瘤小鼠模型的建立及氟尿嘧啶抑瘤作用的免疫机制

目的:建立荷瘤野生型C57BL/6小鼠及C57BL/6裸鼠模型,探讨5-氟尿嘧啶(5-FU)抑瘤作用的免疫机制。方法:给正常野生型C57BL/6小鼠皮下接种小鼠淋巴瘤EL4细胞,建立荷EL4肿瘤的小鼠模型。接种瘤细胞后12d,荷瘤小鼠腹腔单次注射不同剂量的5-FU,找出5-FU可发挥最大的抑瘤作用、并能致使荷瘤小鼠肿瘤消退不再复发的最小使用剂量。遗传背景相同的野生型C57BL/6小鼠及C57BL/6裸鼠同时皮下接种小鼠淋巴瘤EL4细胞,建立两种荷瘤小鼠模型。接种瘤细胞后12d,两种荷瘤小鼠腹腔内同时注射可使野生型C57BL/6荷瘤小鼠肿瘤消退不再复发5-FU的最低剂量,以正常野生型C57BL/6小鼠为对照,观察5-FU对T淋巴细胞缺陷裸鼠的抑瘤作用。结果:以75mg/kg5-FU治疗1周后,两种荷瘤小鼠的肿瘤以相同的速率缩小直至消失。但在5-FU治疗2周后,T淋巴细胞缺陷的C57BL/6裸鼠肿瘤复发,而免疫功能正常的野生型C57BL/6小鼠肿瘤治愈。结论:单一剂量的5-FU对荷淋巴瘤EL4小鼠具有明显的近期治疗效果,5-FU抑瘤作用的发挥不需要T细胞参与;但5-FU抗肿瘤作用的远期疗效与机体T淋巴细胞功能密切相关。

Study of the immunological mechanism of anti-tumor effects of 5-FU by establishing EL4 tumor-bearing mouse models

AIM:To investigate the immunological mechanism of anti-tumor effect of 5-FU by establishing lymphoma EL4 tumor-bearing mouse models in wild type C57BL/6 mice and nude C57BL/6 mice,respectively.METHODS:The mouse lymphoma EL4 cells were inoculated subcutaneously into wild type C57BL/6 mice(immune-competent mice).Twelve days later,5-FU of different doses was administered intraperitoneally to treat these wild type C57BL/6 tumor-bearing mice.The size of tumors in the wild type C57BL/6 mice was observed and recorded to explore the minimal dose of 5-FU that could cure the tumor-bearing mice.Then the same amount of EL4 tumor cells was inoculated subcutaneously into wild type C57BL/6 mice and nude C57BL/6 mice(T cell-deficient mice) simultaneously,which had the same genetic background of C57BL/6.Twelve days later,5-FU of the minimal dose was given intraperitoneally to treat both the wild type and nude C57BL/6 tumor-bearing mice.The size of tumors in the two different types of mice was observed and recorded.RESULTS:A single dose of 5-FU(75 mg/kg) cured both the EL4 tumor-bearing wild type C57BL/6 mice and the EL4 tumor-bearing nude C57BL/6 mice in the first week.Two weeks after 5-FU treatment,all of the nude mice died of tumor relapse while most of the wild type C57BL/6 mice were fully recovered.CONCLUSION:A single dose of 5-FU has marked anti-tumor effects on lymphoma EL4 tumor-bearing C57BL/6 mice with or without T lymphocytes.The relapse of tumors after 5-FU treatment might be related to the function of T lymphocytes.