人参总皂苷调控NK细胞活性促进5-氟尿嘧啶抗肿瘤的作用

Total saponins of Panax ginseng promoting the anticancer activity of 5-Fluorouracil by mediating NK cell activity

目的探讨人参总皂苷(TSPG)调控NK细胞活性促进5-氟尿嘧啶抗肿瘤的作用机制。方法建立小鼠肝脏原位移植瘤模型,随机分为模型组、TSPG组、5-Fu组及TSPG+5-Fu组,给药观察14 d。实验结束分离肝脏并剥离肿瘤,计算肿瘤体积、肿瘤质量、抑瘤率;应用HE染色观察肿瘤组织病理变化;采用免疫组化检测NK细胞在肿瘤组织中的浸润情况;通过流式细胞技术检测肝脏、脾脏中NK细胞含量;应用实时定量PCR检测肿瘤组织中穿孔素、颗粒酶B的mRNA表达水平。结果与模型组比较,各给药组肿瘤体积及质量均显著降低(P<0.05),肿瘤组织出现明显坏死;TSPG组NK细胞在肿瘤组织浸润增加(P<0.05);TSPG组与TSPG+5-Fu组肝脏、脾脏中NK细胞的含量均升高(P<0.05),肿瘤组织中穿孔素、颗粒酶B的mRNA表达水平亦升高(P<0.05)。结论TSPG可以增强5-Fu抗肿瘤的作用疗效,其机制可能与TSPG提高荷瘤小鼠体内NK细胞的数量及杀伤活性有关。

Objective To explore the inhibitory effects of total saponins of Panax ginseng （TSPG） combined with 5-fluorouracil （5-Fu） on orthotopic transplantation tumors and the mechanism. Methods The orthotopic transplantation tumor models were established and randomly divided into 4 groups ： model group, TSPG group, 5-Fu group and TSPG＋ 5-Fu group. After 14 days, the livers were harvested and tumors were separated. The tumor weight, volume and tumor inhibition rate were determined. The pathological changes were observed with HE staining. The infiltration of NK cells in tumor tissues was observed with immunohistochemical method. The proportions of NK cells in the liver and spleen were assessed with flow cytometry. The mRNA expressions of perforin and granzyme B in tumor tissues were detected with real-time PCR. Results Compared with the model group, the other groups had significantly lower/smaller tumor volume and weight （P〈0.05） and more obvious necrosis. The infiltration of NK cells increased in the TSPG group （P〈 0.05）. The proportions of NK cells in the liver and spleen, and the mRNA expressions of perforin and Granzyme B increased in the TSPG group and TSPG＋5-Fu group （P〈0.05）. Conclusion TSPG promotes the antitumor effects of 5-Fu, which may be explained by the increased number of NK cells and cytotoxity.