异种血管内皮生长因子受体重组蛋白疫苗与顺铂联合给药对小鼠LL/2肿瘤的抑制作用

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背景与目的:生物鄄化学治疗是生物治疗与化疗相结合的一种恶性肿瘤综合治疗的新动向之一。抗肿瘤血管形成已成为肿瘤生物治疗的一种策略。本实验观察以重组鹌鹑血管内皮生长因子受体2(quailvascularendothelialgrowthfactorreceptor鄄2,qVEGFR)作为肿瘤疫苗,联合化疗药物顺铂抑制小鼠LL/2肿瘤生长的作用。方法:在C57BL/6小鼠建立LL/2肺癌模型,接种瘤细胞7天后将小鼠随机分成qVEGFR联合顺铂组(简称联合给药组)、qVEGFR组、顺铂组、生理盐水对照组4组。实验中观察肿瘤的生长情况以及小鼠的存活情况和不良反应,并检测小鼠抗自身VEGFR鄄2抗体产生情况、肿瘤微血管密度(microvesseldensity,MVD)、肿瘤细胞凋亡情况等。结果:联合给药组肿瘤明显小于生理盐水对照组,其中有3只小鼠肿瘤完全消退;在接种肿瘤细胞后第70天,联合给药组小鼠存活率为90%,明显高于qVEGFR组(60%)、顺铂组(0%)以及生理盐水对照组(0%)。显微镜下计数结果显示,联合给药组与qVEGFR组所产生的分泌抗qVEGFR抗体的B细胞数量分别为(156.8±19.3)/106个脾细胞和(143.6±18.6)/106个脾细胞。联合给药组肿瘤MVD为11.4±1.3,qVEGFR组为16.4±1.6,顺铂组为33.5±4.5,生理盐水对照组为45.5±4.5,联合给药组MVD明显低于生理盐水对照组。原位末端标记技术 Background and Objective: Biological-chemical therapy is one of the new trends in the comprehensive treatment of malignant tumors combined with biological therapy and chemotherapy. Antitumor vascularization has become a strategy for tumor biotherapy. In this study, recombinant quail vascular endothelial growth factor receptor 2 (quailvascularendothelial growth factor receptor-2, qVEGFR) as a tumor vaccine combined with cisplatin chemotherapy to inhibit tumor growth in mice LL / 2. Methods: LL / 2 lung cancer model was established in C57BL / 6 mice. After being inoculated with tumor cells for 7 days, the mice were randomly divided into qVEGFR combined with cisplatin (qd) group, qVEGFR group, cisplatin group and saline control group group. The growth of the tumor and the survival and adverse reactions of the mice were observed in the experiment. The anti-VEGFR-2 antibodies, the microvessel density (MVD) and the apoptosis of the tumor cells were detected. Results: The tumors in the combination group were significantly smaller than those in the saline control group, of which 3 mice completely regressed. On the 70th day after the tumor cells were inoculated, the survival rate in the combination group was 90%, significantly higher than that in the qVEGFR group (60%), cisplatin group (0%) and saline control group (0%). Counting under the microscope showed that the number of B cells secreting anti-qVEGFR antibody produced by combination therapy group and qVEGFR group were (156.8 ± 19.3) / 106 splenocytes and (143.6 ± 18.6) / 106 splenocytes, respectively. MVD was 11.4 ± 1.3 in the combination group, 16.4 ± 1.6 in the qVEGFR group, 33.5 ± 4.5 in the cisplatin group, and 45.5 ± 4.5 in the saline control group. The MVD in the combination group was significantly lower than that in the saline group. In situ end labeling technology
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