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目的探讨新城疫病毒疫苗(ATV-NDV)和白细胞介素-15(IL-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-NDV 0.2ml;II组注射IL-15100μg/kg;III组注射IL-15 100μg/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-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-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。
Objective To investigate the therapeutic effect and mechanism of Newcastle disease virus vaccine (ATV-NDV) and interleukin-15 (IL-15) on subcutaneous xenografts in 3AO nude mice. Methods The subcutaneous xenograft models of 3AO nude mice were established and randomly divided into 4 groups with 10 in each. Group I was injected with ATV-NDV 0.2ml; Group II with IL-15100μg / kg; Group III with IL-15 100μg / kg plus ATV-NDV 0.2ml; Group IV as control group, intraperitoneal injection of saline Lower extremities subcutaneous injection, IL-15 intraperitoneal injection, formulated according to 0.2ml per nude mouse); Observe the tumor formation rate, survival rate, survival rate and tumor growth curve of nude mice in each group. Flow cytometry (FCM) was used to observe the apoptotic rate and cell cycle of nude mice xenografts, count the double labeled NK cell population, determine the spleen weight of nude mice, Physical examination. Results Compared between the experimental group and the control group, there was a significant difference between the combination therapy group and the single treatment group: survival rate of tumor-bearing nude mice, apoptosis rate of tumor cells, count of NK cells and weight of nude mice. Pathological examination in each treatment group showed tumor necrosis, apoptotic cells, tumor cells and tumor within the obvious lymphocytic infiltration. The spleen of ATV-NDV treatment group had hyperplasia and hypertrophy. The spleen of IL-15 treatment group had congestion and hyperplasia, liver had hepatocyte edema, eosinophilic degeneration and swollen around. The control group nude mice liver, spleen, kidney no significant pathological changes. Conclusion ATV-NDV and IL-15 have significant inhibitory effects on subcutaneous xenografts of human ovarian cancer in nude mice. IL-15 has a synergistic effect on ATV-NDV. Its mechanism and ATV-NDV directly and specifically cytotoxic effect on tumor cells and improve the immunogenicity of tumor antigens; IL-15 enhances the cytotoxic activity of NK cells and induces the production of NK cells and cytokines.