苦参碱对小鼠H22 细胞抗肿瘤作用及其机制研究

目的观察苦参碱在体内和体外的抗肿瘤作用,探讨其可能的作用机制。方法 MTT法检测苦参碱对小鼠腹水瘤细胞H22的体外杀伤作用;通过建立动物肿瘤模型,免疫组化法检测其抑瘤率和肿瘤内血管密度,以及瘤体血管内皮生长因子。结果①体外实验显示,1.0、2.0、4.0mg·mL^-1苦参碱对H22肿瘤细胞的生长均有明显的抑制作用,并呈剂量依赖性,与对照组相比有显著性差异（P〈0.05）。②体内实验显示,苦参碱高、中、低剂量组对小鼠H22实体瘤均有抑制作用,并呈现一定的剂量效应关系,其中苦参碱高剂量组瘤重明显小于空白对照组,高剂量组的抑制作用明显强于中、低剂量组,P〈0.01;③免疫组化结果显示,苦参碱组和环磷酰胺组瘤组织内的VEGF蛋白表达阳性率和平均染色强度均低予对照组,组间有显著差异（P〈0.05）。苦参碱高剂量组MVD明显低于对照组,组间差异性非常显著（P〈0.01）,较环磷酰胺组无显著性差异（P〉0.05）。结论苦参碱能够提高H22肉瘤小鼠生存质量,具有抑制肿瘤新生血管生成的作用,可能是通过降低VEGF蛋白表达来实现的。

Antitumor Effects of Matrine on Murine Hepatocarcinoma Cell Line H22 and the Mechanism

Objective To study the antitumor effects of matrine on murine hepatocarcinoma cell line H22 in vitro and in vivo,and to explore the underlying mechanism.Method Cytotoxicity effect of matrine on cultured H22 cells was determined by MTT assay in vitro.The tumor inhibitory rate and the vascular density were tested in animal tumor model by experimental treatment.The expressions of VEGF were measured by immunohistochemistry.Results The results showed that the matrine of 1.0,2.0,4.0 mg·mL^-1 inhibited the growth of H22 tumor cells significantly in a dose dependent relationship,compared with the control group significantly （P〈0.05）,In vitro;And solid tumors of H22 tumor-bearing mice were inhibited by the high,medium and low dose of matrine in vivo,and have a dose response relationship,in which high dose matrine group tumor weight was significantly lower than the control group（P〈0.05）.The inhibition of high dose matrine group was stronger than the low dose group（P0.01）;Immunohistochemistry showed that matrine group and the cyclophosphamide group within the tumor tissue VEGF protein positive rate and staining intensity were lower than control group,a significant difference between groups （P〈0.05）.MVD matrine high dose group was significantly lower than the control group,with significant difference （P0.01）.While compared with cyclophosphamide,there was no significant difference （P〈0.05）.Conclusion Matrine can improve the quality of 1ife in H22 tumor-bearing mice and inhibit tumor angiogenesis,which is 1ikely to be achieved through reducing VEGF protein expression.