丹参多酚酸盐对裸鼠HCC系人肝癌细胞株SMMC-7721移植瘤的影响

Effect of depsides salts from Salvia miltiorrhiza on human hepatoma cell line SMMC-7721 subcutaneous xenografts in nude mice

目的:观察丹参多酚酸盐对人肝癌细胞株SMMC-7721裸鼠皮下移植瘤的影响,探讨其对肝癌肿瘤的作用机制。方法:建立裸鼠肝癌肿瘤模型,将36只裸鼠(雌雄各半)随机分成6组,每组6只,分别为模型组、阴性对照组(生理盐水组)、阳性对照组(顺铂组)、3种不同质量浓度(10,20,50 mg/kg)的丹参多酚酸盐给药组。在裸鼠长出肉眼可见瘤体后注射丹参多酚酸盐治疗16 d收集皮下肿瘤标本。肿瘤标本进行HE检测观察组织形态变化和免疫组织化学检测血管内皮生长因子(vascular endothelial growth factor,VEGF)和肿瘤增殖抗原Ki67的表达情况,以验证是否抑制肿瘤细胞生长、增殖。结果:各用药组的肿瘤生长受到抑制,肿瘤组织细胞形态较之模型组和阴性对照组呈现皱缩、破碎、不规则排列;且随着给药剂量的增大形态学改变更明显。丹参多酚酸盐给药组和顺铂组的VEGF和Ki67表达量均较模型组和阴性对照组低(P<0.05)。结论:丹参多酚酸盐能抑制裸鼠HCC系人肝癌细胞株SMMC-7721移植瘤的生长,其机制可能与下调Ki67和VEGF有关。

Objective: To exlpore the eff ect of depsides salts from Salvia miltiorrhiza on human hepatoma cell line SMMC-7721 xenograft tumors and the possible mechanisms.Methods: A total of 36 nude mice were divided into 6 groups: A model group, a negative control group, a positive control group, and 3 treatment groups at low, middle or high dose(n=6). The tumor model of nude mice was given depsides salts at a dose of 10, 20 or 50 mg/kg every 3 day for 16 days. Then samples of subcutaneous tumors in nude mice were collected. The morphological changes of tumor samples were observed by HE staining and the expression of vascular endothelial growth factor(VEGF) and the tumor antigen Ki67 was detected by immunohistochemical method.Results: The tumor growth was inhibited by all doses of depsides salts. The morphology of tumors was shrinkage, broken and irregularly arranged compared with the tumors in the model group and the negative control group. Morphological changes were more obvious in tumors with treatment at high dose. Expression of VEGF and Ki67 in treatment groups and the positive control group were lower than that in the model group and the negative control group, with a significant difference(P<0.05).Conclusion: Depsides salts from Salvia miltiorrhiza can inhibit the growth of human hepatoma cell line SMMC-7721 tumor in nude mice, which is related to the inhibition of Ki67 and VEGF.