白细胞介素-15治疗3AO裸鼠移植瘤的实验研究

目的:探讨白细胞介素-15(IL-15)治疗3AO裸鼠皮下移植瘤的效果及其机制。方法:建立3AO裸鼠皮下移植瘤模型,随机分为5组,每组12只。I组为顺铂(cD-DP)3mg/kg;Ⅱ组、Ⅲ组分别为IL-1550μg/kg,100μg/kg;Ⅳ组为cDDP1.5mg/kg加IL-1550μg/kg;Ⅴ组为对照组,注射生理盐水(各组药物均腹腔注射,按每只裸鼠0.2ml配制),1次/d,连用1周。观察移植瘤成瘤率、裸鼠生存期、生存延长率及肿瘤生长曲线。停药1天,1周,2周后,观察移植瘤细胞凋亡率及细胞周期,NK细胞群计数;测定裸鼠脾脏重量;对移植瘤及裸鼠肝、脾、肾行常规病理学检查。结果:实验组与对照组相比荷瘤裸鼠生存延长率,脾脏重量,移植瘤细胞凋亡率,NK细胞群计数均有明显差异。病理学检查示各治疗组均见肿瘤坏死,肿瘤细胞周围及肿瘤内淋巴细胞明显浸润。IL-15治疗组脾脏有充血增生表现,肝脏肝细胞嗜酸性变性,肝细胞水肿,周围有浊肿;cDDP治疗组肾脏近曲小管和远曲小管细胞水肿,管腔变小;对照组裸鼠肝、脾、肾未见明显病理改变。结论:IL-15对人卵巢癌裸鼠皮下移植瘤有明显的抑制作用,其机制可能与IL-15增强NK细胞的细胞毒活性,诱导NK细胞及细胞因子产生有关。

Experimental study on the treatment effect of interleukin-15 to the transplanted tumor in nude mice

Objective:To explore the treatment effect and mechanism of interleukin-15(IL-15)on the subcutaneous transplanted tumor in nude mice.Metheds:The subcutaneous nude mice model were established with human ovarian cancer cell strain 3AO and were randomly assigned to 5 groups,every group had 12 nude mice.Group Ⅰ was injected cisplatin 3mg/kg;Groups Ⅱ,Ⅲ were IL-15 50μg/kg and 100μg/kg respectively;Group IV was IL-15 50μg/kg plus cisplatin 1.5mg/kg simultaneously;Group V was control,injected with normal saline(all the drugs were injected intraperitoneally in 0.2ml per nude mice).The tumor formation rates,survival,survival prolongation rates and the tumor growth curve diagram of each group were observed.The apoptosis,cell cycle and NK cell cluster count of the transplanted tumor were detected.The treated nude mice were executed at the time the drug ceased 1 day,1 week and 2 weeks.The nude mice spleens were weighed and the transplanted tumor,liver,spleen and kidney were checked by routine pathological examination.Results:There were significant differences of the experimental and control groups in the survival prolongation rate,spleen weight of nude mice,tumor cell apoptosis rate and NK cell number.The nude mice in the treated groups could be observed tumor necrosis,and lymphocytes soakage around the tumor cell and in the tumor.Spleen enlargement and congestion,the liver cell acidophilic degeneration,the liver cell hypertrophy,cloudy swelling could be seen in the IL-15 treated groups.The renal tubule cells hypertrophy and the lumina narrowing could be seen in the cisplatin treated group.There were no distinct pathologic changes in the liver,spleen and the kidney of the control group.Conclusion:IL-15 can significantly inhibit the subcutaneous transplanted tumors of nude mice.The mechanism may be that IL-15 induce the NK cell and cytokine generation,and enhance the NK cell cytotoxicity.