肿瘤超声抗原疫苗联合低剂量环磷酰胺在小鼠体内抗肿瘤效应的研究

The anti-tumor effects of the sonicate vaccine combining low dose cyclophosphamide in mice

目的探索肿瘤超声抗原疫苗联合低剂量环磷酰胺(CTX)的抗肿瘤效应。方法 C57BL/6雄性小鼠48只,随机分为PBS对照组、CTX组、FBL3超声抗原疫苗组、FBL3超声抗原疫苗联合CTX组。按程序免疫3次后,每组随机取4只小鼠,流式细胞术比较脾细胞中CD4+CD25+Treg及CD8+T细胞比例,MTT法比较脾细胞杀伤FBL3功能,各组其余小鼠接种FBL3肿瘤细胞,观察成瘤时间及肿块大小。结果超声抗原疫苗不能诱导CD8+T细胞比例升高(P>0.05);CTX可下调Treg细胞数量(P<0.05);疫苗和CTX均可提高脾细胞体外肿瘤杀伤率并能缩小肿块体积、延长小鼠成瘤时间,两者联合显示更强的抗肿瘤效应。结论肿瘤超声抗原疫苗联合小剂量CTX可能通过提高体液免疫或固有免疫发挥抗肿瘤效应。

To investigate the anti-tumor effects of the sonicate antigen of FBL3 combined with low-dose cyclophosphamide（CTX）,48 male C57BL/6 mice were randomly divided into four groups：PBS control group,CTX group,FBL3 sonicate antigen vaccine group and FBL3 vaccine combining CTX group.After three times of immunization,4 mice were sacrificed in every group randomly,and their spleen cells were obtained for detecting the ratio of CD4＋CD25＋Treg cells and CD8＋T cells to total lymphocytes by flow cytometry,and testing the cytotoxic activity of spleen cells to FBL3 by 3-2,5-diphenyl-tetrazolium bromide（MTT） test.The other mice in every group were injected subcutaneously with FBL3 cells,and the growth rate and volume of tumor were observed and recorded.The results showed sonicate antigen vaccine alone could not increase the CD8＋T ratio,while CTX alone could reduce the number of Tregs;when the vaccine was used in combination with CTX,it can enhance the cytotoxicity of spleen cells and delay formation of tumor,showing better anti-tumor effects.In conclusion,the antitumor synergism of the tumor sonicate antigen vaccine and low dose CTX may be gained through increasing humoral immunity or inherent immunity.