文献类型：期刊文献

英文题名：Elucidation of the anti-gastric cancer mechanism of Guiqi Baizhu Formula by integrative approach of chemical bioinformatics

作者：Wang, Yanru[1];Li, Jiawei[1];Liu, Xiuzhu[1];Zhang, Yixi[2];Wang, Chao[3];Guo, Qingyang[1];Wang, Yan[4];Jiang, Bing[4];Jin, Xiaojie[1,2,4,5];Liu, Yongqi[1,4,5]

第一作者：王云荣

通信作者：Jin, XJ[1];Liu, YQ[1]

机构：[1]Gansu Univ Chinese Med, Gansu Univ, Key Lab Mol Med & Chinese Med Prevent & Treatment, Lanzhou 730000, Peoples R China;[2]Gansu Univ Chinese Med, Coll Pharm, Lanzhou 730000, Peoples R China;[3]Shanxi Datong Univ, Coll Med, Datong 037000, Peoples R China;[4]Gansu Univ Chinese Med, Lanzhou 730000, Peoples R China;[5]Minist Educ Peoples Republ China, Key Lab Dunhuang Med & Transformat, Lanzhou 730000, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Gansu Univ Chinese Med, Lanzhou 730000, Peoples R China.|[10735]甘肃中医药大学;

年份：2024

卷号：134

外文期刊名：INTERNATIONAL IMMUNOPHARMACOLOGY

收录：;Scopus(收录号：2-s2.0-85192719751);WOS:【SCI-EXPANDED(收录号:WOS:001242528700001)】；

基金：Funding This study was supported by the National Natural Science Founda- tion of China (82360864, 81960869 and 82160896) , and Research project of traditional Chinese medicine in Gansu province (GZKP-2022- 38) .

语种：英文

外文关键词：Guiqi Baizhu Formula; Gastric cancer; Glycyrol; Emodin; IGF1R/PI3K/PDK1; VEGFR2

摘要：Gastric cancer (GC) has posed a great threat to the lives of people around the world. To date, safer and more costeffective therapy for GC is lacking. Traditional Chinese medicine (TCM) may provide some new options for this. Guiqi Baizhu Formula (GQBZF), a classic TCM formula, has been extensively used to treat GC, while its bioactive components and therapeutic mechanisms remain unclear. In this study, we evaluated the underlying mechanisms of GQBZF in treating GC by integrative approach of chemical bioinformatics. GQBZF lyophilized powder (0.0625 mg/mL, 0.125 mg/mL) significantly attenuated the expression of p-IGF1R, PI3K, p-PDK1, p-VEGFR2 to inhibit the proliferation, migration and induce apoptosis of gastric cancer cells, which was consistent with the network pharmacology. Additionally, atractylenolide I, quercetin, glycyrol, physcione and aloe-emodin, emodin, kaempferol, licoflavone A were found to be the key compounds of GQBZF regulating IGF1R and VEGFR2, respectively. And among which, glycyrol and emodin were determined as key active compounds against GC by farther vitro experiments and LC/MS. Meanwhile, we also found that glycyrol inhibited MKN-45 cells proliferation and enhanced apoptosis, which might be related to the inhibition of IGF1R/PI3K/PDK1, and emodin could significantly attenuate the MKN-45 cells migration, which might be related to the inhibition of VEGFR2-related signaling pathway. These results were verified again by molecular dynamics simulation and binding interaction pattern. In summary, this study suggested that GQBZF and its key active components (glycyrol and emodin) can suppress IGF1R/PI3K/PDK1 and VEGFR2-related signaling pathway, thereby inhibiting tumor cell proliferation and migration and inducing apoptosis. These findings provided an important strategy for developing new agents and facilitated clinical use of GQBZF against GC.