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

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

Antitumor effects of recombinant quail vascular endothelial growth factor receptor 2, as a vaccine, combined with cisplatin on LL/2 tumor model in mice

BACKGROUND & OBJECTIVE: Bio-chemotherapy is a new trend in cancer therapy. Antiangiogenic therapy represents a new strategy of tumor biotherapy. This study was designed to explore antitumor effect of recombinant quail vascular endothelial growth factor receptor 2 (qVEGFR) combined with cisplatin. METHODS: Lewis lung carcinoma model (LL/2) was established in C57BL/6 mice. Seven days after inoculation of tumor cells, mice were randomized into combination group, qVEGFR group, chemotherapy group, and normal saline (NS) group (10 mice/group), and received relevant treatments. Tumor growth, survival rate of mice, and side effects were observed. Anti-VEGFR-2 antibody-producing B cells (APBCs) was detected by enzyme-linked immunospot (ELISPOT), microvessel density (MVD) of tumor was detected by immunohistochemistry, and tumor cell apoptosis was also detected. RESULTS: Tumor volume of mice was obviously smaller in combination group than in NS group. Complete regression of tumor growth was observed in 3 of the 10 mice in combination group. Seventy days after inoculation of tumor cells, survival rate of mice was significantly higher in combination group than in qVEGFR, cisplatin, and NS groups (90% vs. 60%, 0%, and 0%, P < 0.05). APBCs counts were (156.8+/-19.3)/10(6) spleen cells in combination group, and (143.6+/-18.6)/10(6) spleen cells in qVEGFR group. MVD was significantly lower in combination group than in cisplatin, and NS groups (11.4+/-1.3 vs. 33.4+/-4.5, and 45.5 +/- 4.5, P < 0.01), MVD in qVEGFR group was 16.4+/-1.6. Tumor cell apoptosis was significantly higher in combination group than in qVEGFR, cisplatin, and NS groups [(36.2+/-3.5)% vs. (15.4+/-2.4)%, (17.6+/-2.6)%, and (4.1+/-1.4)%, P < 0.05]. CONCLUSION: The combination therapy of qVEGFR and cisplatin has synergistic antitumor effect.