GnRH/M_2与mGM-CSF/βhCG融合蛋白致敏树突状细胞疫苗抗小鼠前列腺癌的作用

Anti-tumor Effect of Dentritic Cells Vaccine Sensitized by GnRH/M_2 and mGM-CSF/βhCG Fusion Proteins on Prostatic Cancer in Mice

目的探讨分别负载GnRH/M_2融合蛋白和mGM-CSF/βhCG融合蛋白的树突状细胞(dendritic cells,DCs)及与多西他赛(DTX)联合应用治疗小鼠前列腺癌的效果,及其抗肿瘤作用机制。方法用GnRH/M_2融合蛋白与mGM-CSF/βhCG融合蛋白分别致敏DC,获得DC疫苗,流式细胞仪检测DC成熟度。测量各组小鼠肿瘤生长体积和重量、检测免疫小鼠脏器指数和脾细胞增殖,脾细胞对癌细胞特异性杀伤活性及小鼠外周血内细胞因子IFN-γ浓度,观察各组对荷瘤小鼠的抑瘤效果。结果与0.9%氯化钠溶液对照组比较,单独用药对荷瘤小鼠肿瘤均具有抑制作用,差异有统计学意义(P<0.05),联合应用组抗肿瘤效果均优于DC疫苗单独应用组(P<0.01)。结论两种DC疫苗均能与多西他赛发挥协同抗前列腺癌作用,抑瘤效果显著增强。且联合应用也能有效抑制前列腺癌细胞RM-1荷瘤小鼠肿瘤的生长。

Objective To investigate the anti-tumor effect of dendritic cells（DCs） vaccines loaded with the GnRH/M_2 or mGM-CSF/βhCG fusion proteins and the co-administration of docetaxel（DTX） on prostatic cancer in mice separately, and to study the mechanism of anti-tumor preliminarily. Methods The dendritic cells were sensitized by the GnRH/M_2 and mGM-CSF/βhCG fusion proteins to obtain DC vaccines respectively. Then, the maturity of DC was detected by flow cytometry. After that, the tumor volume and weight of each group were measured, as well as the visceral index and the splenocyte proliferation of each mouse were detected. Moreover, spleen cells cytotoxicity was detected. Finally, the concentration of IFN-γ in the peripheral blood was measured, and the tumor-inhibiting effect of each immunized group was observed. Results The difference between each dendritic cell vaccines and the normal saline group was statistically significant（P〈0.05）. Moreover, the anti-tumor effects of co-administration groups were found better than each dendritic cell vaccine group（P〈0.01）. Conclusion The co-administration of each dendritic cell vaccines and DTX could effectively inhibit the growth of prostate tumor in mice. Besides, the co-administration of two dendritic cell vaccines could also enhance tumor-inhibiting effect.