基于网络药理学的补肾健脾方治疗肝癌的作用机制研究  

Effective mechanism of Bushen Jianpi Decoction in the treatment of liver cancer based on network pharmacology

作　　者：武容 李晓燕[1] 蔡菲菲[1] 陈晓乐[1] 杨梦蝶 潘秋莎 陈启龙[1] 苏式兵[1] WU Rong;LI Xiao-yan;CAI Fei-fei;CHEN Xiao-le;YANG Meng-die;PAN Qiu-sha;CHEN Qi-long;SU Shi-bing(Research Center for Traditional Chinese Medicine Complexity System,Shanghai University of Chinese Medicine,Shanghai 201203,China)

机构地区：[1]上海中医药大学中医复杂系统研究中心,上海201203

出　　处：《中华中医药杂志》2018年第9期4134-4139,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金委员会重点项目(No.81330084);上海市教委E-研究院中医内科建设计划资助项目(No.E03008)~~

摘　　要：目的:探讨补肾健脾方治疗肝癌的分子机制。方法:利用网络药理学技术筛选补肾健脾方治疗肝癌关键成分及靶标。采用MTS法检测肝癌HepG2细胞活力;MuseTM Cell Analyzer检测细胞凋亡;蛋白免疫印迹法检测核心靶标蛋白的表达。结果:利用相关数据库及拓扑分析共筛选出9个化合物、56个靶标及10条信号通路。与空白血清组及正常对照组比较,20%补肾健脾方含药血清在48h和72h明显抑制HepG2细胞的存活率(P<0.05),并在48h能够诱导HepG2细胞凋亡(P<0.05)。同时补肾健脾方组能抑制了PI3K、P-Akt及BCLXL的表达,增加了p53、Cleaved CASP9与Cleaved CASP3的表达(P<0.05,P<0.01)。结论:补肾健脾方通过调节复杂分子网络对肝癌起到治疗作用,其部分作用机制可能与调控PI3K/Akt/mTOR信号通路,诱导细胞凋亡,从而抑制肝癌细胞的生长相关。Objective： To investigate the effective mechanisms of Bushen Jianpi Decoction （BJD） in the treatment of the liver cancer. Methods： The compound-target-disease complex molecular networks of BJD were constructed and critical therapeutic compounds and corresponding targets for liver cancer treatment were screened respectively. MTS was applied to detect the HepG2 cells vitality. MuseTM Cell Analyzer was used to assay the apoptosis. Western blot was used to detect the expressions of potential target proteins. Results： Compounds of BJD were collected from relative databases and network topology analysis. The results that suggested 9 compounds 56 targets and 10 pathways were important. Compared to normal the serum group and normal control group, drug serum with 20%BJD inhibited the proliferation of HepG2 cells significantly at 48h and 72h （P〈0.05）, induced the apoptosis of HepG2 cells significantly at 48h （P〈0.05） and reduced the levels of PI3K, P-Akt, and BCLXL expressions, increased the levels of p53, Cleaved CASP9 and Cleaved CASP3 expressions significantly （P〈0.05, P〈0.01）. Conclusion： BJD can play a role in the treatment of liver cancer by regulating the complex molecular network. Its mechanism may be related to the regulation of PI3K/AkffmTOR signaling pathway, inducing cell apoptosis and inhibiting the growth of hepatoma cells.

关 键 词：补肾健脾汤 网络药理学 肝癌 分子机制 细胞凋亡 P13K/Akt/mTOR信号通路 

分 类 号：R285[医药卫生—中药学]