白花蛇舌草对人肝癌HepG2细胞裸鼠皮下移植瘤PI3K/Akt信号通路的影响

Effect of Hedyotis Diffusa Willd on PI3K/Akt Pathway in Nude Mice Implanted Hepatoma HepG2 Cells

目的探讨白花蛇舌草对人肝癌HepG2细胞裸鼠皮下移植瘤组织磷酸酰肌醇3激酶(PI3K)、总蛋白激酶B(Akt)和磷酸化Akt(p-Akt)蛋白表达的影响。方法建立肝癌裸鼠皮下移植瘤模型,随机分为药物组(6 g·kg-1·d-1白花蛇舌草灌胃)和模型组(同等体积生理盐水灌胃),连续给药4周后处死,观察抑瘤率;免疫组织化学染色检测肿瘤组织PI3K、总Akt和p-Akt蛋白的表达。结果与模型组比较,药物组瘤体质量明显下降(t=4.270,P=0.006),抑瘤率达61.29%;PI3K蛋白表达灰度值从82.00±2.72升高至118.67±8.44(t=0.209,P=0.049);Akt蛋白表达灰度值从72.37±2.89升高至105.19±4.718(t=2.050,P<0.001),p-Akt蛋白表达灰度值从87.99±4.16升高至96.34±5.72(t=4.123,P=0.002),提示PI3K、Akt和p-Akt的蛋白表达水平均较模型组明显减低。结论白花蛇舌草通过可调控PI3K/Akt信号通路的相关蛋白抑制肿瘤血管新生。

Objective To evaluate the effect of hedyotis diffusa willd on phosphoinositide 3 kinase （ PI3K）, pro- tein kinase B （Akt） protein and phosphorylated Akt （p-Akt） protein expressions in nude mice with hepatic carci- noma transplanted subcutaneously. Methods Nude mice xenografts were established. The mice were randomly divid- ed into 2 groups： the hedyotis diffusa willd group and the vehicle group, which received hedyotis diffusa willd （6 g · kg ^-1· d^-1, intragastric administration ） and normal saline （ intragastric administration ）, respectively. After 4 weeks of treatment,the tumors were harvested and weighed. The levels of PI3K, Akt and p-Akt proteins were ob- served with immunohistochemical staining. Results The tumor weight of the hedyotis diffusa willd group were high- er than that of the vehicle group （t = 4.270, P = 0. 006）. The gray levels of PI3K, Akt and p-Akt in the hedyotis dif- fusa willd group （118.67 ± 8.44,105.19 ± 4. 718,96.34 ± 5.72） were also higher than those in the vehicle group （82.00±2.72,72.37±2.89,87.99 ±4. 16） （t=0.209,P=0.049; t=2.050,P〈0.001; t=4.123,P= 0. 002）. The expressions of PI3K, Akt and p-Akt proteins were suppressed significantly by hedyotis diffusa willd. Conclusion Hedyotis diffusa willd could inhibit angiogenesis in hepatocellular carcinoma via regulating the PI3K/Akt pathway.