蝎毒多肽提取物对小鼠Lewis肺癌免疫逃逸的影响

Effect of polypeptide extract from scorpion venom(PESV) on immune escape of Lewis lung carcinomas

目的:观察蝎毒多肽提取物(PESV)对Lewis肺癌(LLC)免疫逃逸的影响。方法:取40只C57BL/6J小鼠,右腋下接种Lewis肺癌细胞悬液,建立皮下种植瘤模型,随机分为荷瘤对照组和PESV治疗组,连续灌胃给予PESV 18 d,检测肿瘤体积并计算抑瘤率;免疫组化法和ELISA法分别检测瘤组织及血清中血管内皮生长因子(VEGF)、转化生长因子β1(TGF-β1)和白介素10(IL-10)的表达,免疫组化法和流式细胞仪分别检测肺癌组织中浸润的DC表面共刺激分子CD80,CD86的表达。结果:PESV抑瘤率为56.60%。与荷瘤对照组相比,瘤组织和血清中VEGF,TGF-β1和IL-10的表达明显降低(P<0.05),DC共刺激分子CD80,CD86的表达明显增加(P<0.05)。结论:PESV可干预肺癌免疫逃逸,其机制可能与减少肿瘤微环境中VEGF,TGF-β1和IL-10的表达,增加DC共刺激分子CD80,CD86的表达有关。

Objective： To study the effects of polypeptide extract from scorpion venom（PESV） on immune escape of Lewis lung carcinomas（LLC） and its mechanism.Method： Forty C57BL/6J mice were inoculated with LLC cells suspension（1×107 cells/mL） in right armpit subcutaneously.The tumor-bearing mice were randomly divided into two groups： the control group and the PESV group.PESV was intragastrically subjected to the mice of the experimental group for 18 days.The tumor volume and tumor inhibitory rate were determined.The expression levels of VEGF,TGF-β1 and IL-10 in tumor microenvironment were determined by immunohistochemistry-staining and ELISA.Surface co-stimulatory molecules CD80 and CD86 of tumor infiltrating dendritic cells（DC） were determined by immunohistochemistry-staining and flow cytometry.Result： The growth inhibitory rate of PESV was 56.60%.The expression levels of VEGF,TGF-β1 and IL-10 were decreased in tumor and serum,while the expression of co-stimulatory molecules CD80 and CD86 on DC were increased in tumor.Compared with the control group,the differences were all significant（P0.05）.Conclusion： PESV was effective in recovering immuno-surveillance and intervening immune escape of lung cancer through multi-pathway.And its effects might be attained by decreasing the level of VEGF,TGF-β1 and IL-10 in tumor microenvironment and increasing the expression of co-stimulatory molecules CD80 and CD86 on DC.