鞣花酸抗S180,H22肿瘤及其抑制新生血管机制探讨  

Antitumor Effect of Ellagic Acid Against S180-and H22-bearing Mice and Possible Mechanism of Anti-angiogenesis

作　　者：于娅[1] 李利民[2] 潘嘉[2] 吴建明[3] 邹文俊[1] 

机构地区：[1]成都中医药大学药学院,成都610075 [2]四川省中医药科学院,成都610041 [3]泸州医学院药学院,四川泸州646000

出　　处：《中国实验方剂学杂志》2015年第8期145-150,共6页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：四川省科技厅项目(2012JY0037)

摘　　要：目的:观察鞣花酸对S180,H22荷瘤小鼠肿瘤生长及微血管生成的影响,以及对血小板衍生因子B(PDGFB),转录激活因子-3(STAT3)及磷酸化STAT3(p-STAT3)基因和蛋白表达的影响,探讨其抗血管生成作用可能的机制。方法:SPF级昆明种小鼠100只,建立S180,H22皮下荷瘤小鼠2种模型,分别随机分为模型组(0.5%CMC溶液)、环磷酰胺组(阳性药,20μg·g-1·d-1)、鞣花酸高、中、低(200,100,50μg·g-1·d-1)剂量组,每组10只,连续给药ig 10 d,观察鞣花酸对荷瘤小鼠肿瘤生长、体重、胸腺指数及脾脏指数,免疫组化法检测肿瘤微血管密度,PDGFB,STAT3及p-STAT3的表达情况。结果:鞣花酸高、中、低剂量组对S180小鼠抑瘤率分别为35.3%,10.6%,5.6%,对H22小鼠抑瘤率分别为36.3%,38.8%,20.6%,其对小鼠体重无明显影响;与模型组比较,高剂量组对S180,H22小鼠脾脏指数较模型组明显上升(P<0.05),鞣花酸高、中剂量组能明显降低S180,H22小鼠肿瘤微血管密度(P<0.05),鞣花酸高、中、低剂量组在S180,H22 2种瘤体中PDGFB,STAT3和pSTAT3的表达明显降低。结论:鞣花酸抑制S180,H22荷瘤小鼠肿瘤生长及微血管形成,其机制可能与下调肿瘤组织中PDGFB表达并抑制下游STAT3的蛋白表达及磷酸化有关。Objective： To observe the antitumor and anti-angiogenesis effect of ellagic acid against the transplantation tumor of S180 and H22 in mice, and to explore its possible mechanism by investigating the protein expressions of platelet-derived growth factor-B （PDGFB）, signal transducer and activator of transcription-3 （STAT3） and p-STAT3 in vivo. Method： Mice bearing S180 and H22 ceils were randomly divided into 5 groups： the model group （5% CMC）, the cyclophosphamide group （20 μg·g^-1·d^-1）, the high-, middle- and low-dose ellagic acid groups （200, 100, 50μg·g^-1·d^-1. The mice were administrated with corresponding medicines for successive 10 days. The tumor inhibitory ratios, body weight, the thymus and spleen index were measured, respectively. The effect on microvascular density, PDGFB, p-STAT3 and STAT3 expressions were detected by using an immunohistochemicalassay assay. Result： The tumor inhibitory ratios of the high-, middle- and low-dose ellagic acid were 35.3% , 10.6% and 5.6% on S180-bearing mice, and 36.3% , 38.8% , 20.6% on H22- bearing mice. While, no significant influence on the body weight was found. Compared with the model group, the spleen index was higher in the high- dose group （P 〈 0.05） , and the microvascular density were lower in the high- and middle-dose groups （P 〈 0.05） , the expressions of PDGFB, p-STAT3 and STAT3 were lower in all doses of ellagic acid groups. Conclusion： Ellagic acid could inhibit the tumor growth and angiogenesis against the transplantation tumor of S180, H22 effectively. Its mechanism may be related to decreasing expression of PDGFB and further the expression and the phosphorylation of STAT3.

关 键 词：鞣花酸 S180 H22 肿瘤生长 血管生成 血小板衍生因子B 转录激活因子-3 磷酸化STAT3 

分 类 号：R285.5[医药卫生—中药学]