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  

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

作　　者：李墨林[1] 李传刚[2] 舒晓宏[3] 李明霞[4] 贾玉杰[1] 秦志海 

机构地区：[1]大连医科大学基础医学院病理生理学教研室,辽宁大连116027 [2]大连医科大学附属二院外科,辽宁大连116027 [3]大连医科大学药学院,辽宁大连116027 [4]解放军第210医院外科,辽宁大连116001 [5]德国洪堡大学CBF肿瘤免疫实验室,德国柏林12200

出　　处：《细胞与分子免疫学杂志》2007年第11期1010-1013,共4页Chinese Journal of Cellular and Molecular Immunology

基　　金：国家留学基金及辽宁省自然科学基金资助(20062156)

摘　　要：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。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 （ immunecompetent 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 tumorbearing 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 （7.5 mg/kg） cured both the EL4 tumorbearing 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.

关 键 词：淋巴瘤EL4细胞 5-氟尿嘧啶(5-FU) C57BL/6小鼠 T淋巴细胞 

分 类 号：R392.12[医药卫生—免疫学]