新城疫病毒疫苗和IL-15治疗3AO裸鼠移植瘤实验研究

目的探讨新城疫病毒疫苗（ATV一NDV）和白细胞介素-15（IL一15）对3AO裸鼠皮下移植瘤的治疗作用及其机制。方法建立3AO裸鼠皮下移植瘤模型，随机分为4组，每组10只。Ⅰ组注射ATV一NDV0．2ml；Ⅱ组注射IL一151001xg／kg；Ⅲ组注射IL-151001zg／kg加ATV—NDV0．2ml；Ⅳ组为对照组，腹腔注射生理盐水（ATV—NDV右侧下肢皮下注射，IL-15腹腔注射，按每只裸鼠0．2ml配制）；观察各组裸鼠成瘤率、生存期和生存延长率及肿瘤生长曲线。流式细胞术（FCM）观察裸鼠移植瘤细胞凋亡率及细胞周期，双标记NK细胞群计数；测定裸鼠脾脏重量；移植瘤瘤体及各组裸鼠肝、脾、肾行常规病理学检查。结果实验组与对照组之间，联合治疗组与单独治疗组之间相比：荷瘤裸鼠生存延长率，移植瘤细胞凋亡率，NK细胞群计数。裸鼠脾脏重量具有明显差异。病理学检查各治疗组中均可见肿瘤坏死，凋亡细胞，肿瘤细胞周围及肿瘤内有明显的淋巴细胞浸润。ATV—NDV治疗组脾脏有增生，肥大。IL—15治疗组脾脏有充血增生，肝脏有肝细胞水肿，嗜酸性变性，周围有浊肿。对照组裸鼠肝、脾、肾未见明显病理改变。结论ATV—NDV、IL-15对人卵巢癌裸鼠皮下移植瘤具有明显抑制作用，IL-15对ATV一NDV有协同作用。其机制与ATV—NDV直接、特异地对肿瘤细胞产生细胞毒作用，提高了肿瘤抗原的免疫原性；IL一15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。

Effect of Newcastle disease virus vaccine and interleukin-15 on transplanted tumor in nude mice in vivo

Objective To discuss the effect and mechanism of Newcastle disease virus vaccine （ATV-NDV） and interleukin-15 （IL-15） on the subcutaneous transplanted tumor in nude mice. Metheds The subcutaneous nude mice model were estabhshed with human ovarian cancer cell strain 3AO and were randomly divided into 4 groups each consisted of 10 nude mice. Mice in Ⅰ group were injected with 0.2ml ATV-NDV; Ⅱgroup were given IL-15 100lxg/kg; Ⅲ group IL-15 100μg/kg＋0.2ml ATV-NDV simultaneously and IV group were controls intraperitoneally given normal saline and 0.2ml （ATV-NDV was given at the right cmra subcutaneously,IL-15 were given intraperitoneally with 0.2ml per nude mice. Results There significant difference among the experimental groups,control group,combining treated group and the singly treated group in survival prolongation rate, spleen weigh of nude mice, tumor cell apoptosis rate and NK cell number were observed. Tumor necrosis,apoptosis,and lymphocytes soakage around the tumor cell and in the tumor, nude mice in the experimental groups could be observed Hyperplasia and hypertrophy of the spleen could be observed in nude mice treated with ATV-NDV. Spleen hyperplasia and congestion, the liver cell acidophilic degeneration, the liver cell hypertrophy, cloudy swelling could be seen in the IL-15 treating groups. There were no distinct pathologic changes in the liver,spleen and the kidney of nude mice in control group. Conclusion The ATV-NDV and IL-15 can all significantly inhibit the subcutaneous transplanted tumors of the nude mice. IL-15 can be a adjuvant to ATV-NDV. The mechanism may be that ATV-NDV can directly and specially generate cytotoxinic effect to the tumor cell and can strengthen the antigennicity of tumor antigen, IL-15 can induce the NK cell and cytokine generation,it can also enhance the NK cell cytotoxicity.