龙胆苦苷对H_(22)肝癌小鼠肿瘤生长抑制及抗血管生成的分析  

Inhibitory effect of gentiopicroside on tumor growth and anti-angiogenesis in mice with H_(22) hepatocellular carcinoma

作　　者：张志恒 贾海燕 崔朝初[2] 张莹雪 ZHANG Zhiheng;JIA Haiyan;CUI Chaochu;ZHANG Yingxue(Department of Oncology in Liaocheng Traditional Chinese Medicine Hospital,Liaocheng 252000,China;Medical College of Henan University of Science and Technology,Luoyang 471000;School of Pharmacy,Shandong University of Traditional Chinese Medicine,Jinan 250355)

机构地区：[1]聊城市中医医院肿瘤科,山东聊城252000 [2]河南科技大学医学院,河南洛阳471000 [3]山东中医药大学药学院,济南250355

出　　处：《中国比较医学杂志》2021年第10期42-47,共6页Chinese Journal of Comparative Medicine

基　　金：河南省科技重点攻关项目(102102310063);河南科技大学研究生创新基金(XJJ-YJS-Z027)。

摘　　要：目的探讨龙胆苦苷对H22肝癌小鼠肿瘤生长的抑制作用及抗血管生成机制。方法右腋皮下注射H_(22)细胞悬液建立H22肝癌小鼠模型,并随机分为模型组、龙胆苦苷低、高剂量组(50 mg/kg、100 mg/kg)及环磷酰胺组(20 mg/kg),每组10只;另选取10只健康小鼠,作为正常组;给药14 d后,检测体重、瘤重、抑瘤率、胸腺指数、脾指数、血清干扰素-γ(IFN-γ)、白细胞介素-2(IL-2)含量及瘤组织碱性成纤维生长因子(b FGF)、转化生长因子-β(TGF-β)、血管内皮生长因子(VEGF)、磷酸化磷脂酰肌醇-3激酶(p-PI3K)及磷酸化蛋白激酶B(p-Akt)表达水平。结果与H22肝癌模型组比较,龙胆苦苷低、高剂量组小鼠体重无明显变化(P>0.05),而瘤重明显降低(P<0.01),其抑瘤率分别为30.43%及42.93%;与H22肝癌模型组比较,龙胆苦苷低、高剂量组小鼠胸腺指数、脾指数及血清IFN-γ、IL-2含量明显升高(P<0.05或P<0.01),而瘤组织b FGF、TGF-β、VEGF、p-PI3K及p-Akt表达明显降低(P<0.05或P<0.01)。结论龙胆苦苷对H_(22)肝癌小鼠肿瘤生长及血管生成均有抑制作用,该作用与提高免疫力,增加血清IFN-γ、IL-2含量及抑制PI3K/Akt信号通路的活化有关。Objective To study the inhibitory effects of gentiopicroside on tumor growth and anti-angiogenesis in mice with H_(22) hepatocellular carcinoma.Methods A H_(22) hepatocellular carcinoma mouse model was established by subcutaneous injection of a H22 cell suspension into the right axilla.Mice with H_(22) hepatocellular carcinoma were randomly divided into a model group,low and high dose gentiopicroside groups(50 and 100 mg/kg,respectively),and a cyclophosphamide group(20 mg/kg)with 10 mice in each group.Another 10 healthy mice were used as the normal group.After 14 days of administration,body weight,tumor weight,tumor inhibition rate,thymus index,spleen index,serum IFN-γand IL-2 contents,and expression levels of b FGF,TGF-β,VEGF,p-PI3K,and p-Akt were measured in tumor tissues.Results Compared with the H22hepatocellular carcinoma model group,the body weights of mice in low and high dose groups of gentiopicroside did not change significantly(P>0.05),while the tumor weight was reduced significantly(P<0.01),with the tumor inhibition rates of 30.43%and 42.93%,respectively.Compared with the H_(22) hepatocellular carcinoma model group,the thymus index,spleen index,and serum IFN-γand IL-2 contents of mice in low and high dose gentiopicroside groups were increased significantly(P<0.05 or P<0.01),while expression of b FGF,TGF-β,VEGF,p-PI3K,and p-Akt in tumor tissues was decreased significantly(P<0.05 or P<0.01).Conclusions Gentiopicroside has an inhibitory effect on tumor growth and anti-angiogenesis effect in H_(22) hepatocellular carcinoma mice,which is related to improving immunity,increasing serum IFN-γand IL-2 levels,and inhibition of activation of the PI3K/Akt signaling pathway.

关 键 词：龙胆苦苷 肿瘤生长 血管生成 肝癌 

分 类 号：R-33[医药卫生]