文献类型：期刊文献

英文题名：Licoflavone A Suppresses Gastric Cancer Growth and Metastasis by Blocking the VEGFR-2 Signaling Pathway

作者：Hongxia, Gong[1,2,3,4];Xiaojie, Jin[1,5];Guangxian, Leng[6];Min, Zhang[1,5];Shiwei, Niu[1,4];Wangjie, Cao[1,2,3,4];Han, Zhang[1,4];Yuanding, Zeng[1,4];Chenghao, Li[1,4];Yaling, Li[1,2,4];Yun, Su[1,2,3,4];Yongqi, Liu[1,2,4]

第一作者：龚红霞;Hongxia, Gong

通信作者：Yun, S[1];Yongqi, L[1];Yun, S[2];Yongqi, L[2];Yun, S[3];Yun, S[4];Yongqi, L[4]

机构：[1]Gansu Univ Chinese Med, Key Lab Mol Med & Chinese Med Prevent & Treatment, Lanzhou 730000, Gansu, Peoples R China;[2]Tradit Chinese Med, Key Lab Prevent & Treatment Chron Dis, Lanzhou 730000, Gansu, Peoples R China;[3]NHC Key Lab Diag & Therapy Gastrointestinal Tumor, Lanzhou 730000, Gansu, Peoples R China;[4]Gansu Univ Chinese Med, Key Lab Dun Huang Med & Transformat, Minist Educ, Lanzhou 730000, Gansu, Peoples R China;[5]Gansu Univ Chinese Med, Coll Pharm, Lanzhou 730000, Gansu, Peoples R China;[6]Lanzhou Univ, Second Clin Med Coll, Lanzhou 730000, Gansu, 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, Key Lab Mol Med & Chinese Med Prevent & Treatment, Lanzhou 730000, Gansu, Peoples R China;[2]corresponding author), Tradit Chinese Med, Key Lab Prevent & Treatment Chron Dis, Lanzhou 730000, Gansu, Peoples R China;[3]corresponding author), NHC Key Lab Diag & Therapy Gastrointestinal Tumor, Lanzhou 730000, Gansu, Peoples R China;[4]corresponding author), Gansu Univ Chinese Med, Key Lab Dun Huang Med & Transformat, Minist Educ, Lanzhou 730000, Gansu, Peoples R China.|[10735]甘肃中医药大学;

年份：2022

卷号：2022

外文期刊名：JOURNAL OF ONCOLOGY

收录：;Scopus(收录号：2-s2.0-85129939850);WOS:【SCI-EXPANDED(收录号:WOS:000795691100001)】；

基金：We acknowledge the Key Laboratory for Molecular Medicine and Chinese Medicine Prevention and Treatment of Major Diseases and Key Laboratory of Dun Huang Medical and Transformation of Ministry of Education of The People's Republic of China at the Gansu University of Chinese Medicine for providing support and assistance for this article. This research was funded by the National Natural Science Foundation of China (No. 81960869), Provincial Key Talent Project (No. GZT2020-9-1), the Innovation Capacity Improvement Project of Colleges and Universities in Gansu Province (No. 2020A-072), the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (No. 2019PT320005), and "Double First-Class" Key Scientific Research Project of Gansu Province (No. GSSYLXM-05).

语种：英文

摘要：Objectives. Licoflavone A (LA) is a natural flavonoid compound derived from the root of Glycyrrhiza. This study investigated the antitumor effect and underlying molecular mechanisms of LA against gastric cancer (GC) in vitro and in vivo. Materials and Methods. A CCK8 assay was used to measure the antiproliferative activity of LA in human GC SGC-7901, MKN-45, MGC-803 cells, and human GES-1 cells. Target prediction and protein-protein interaction (PPI) analysis were used to identify the potential molecular targets of LA. The binding pattern of LA to VEGFR-2 was analyzed by molecular docking and molecular dynamic (MD). The affinity of LA for VEGFR-2 was determined by microscale thermophoresis (MST). The protein tyrosine kinase activity of VEGFR-2 in the presence of LA was determined by an enzyme activity test. The effect of LA on the proliferation of VEGF-stimulated MKN-45 cells was measured with CCK8 assays, clone formation assays, and 3D microsphere models. Hoechst 33342 staining, FCM, MMP, and WB assays were used to investigate the ability of LA to block cell cycle and promote apoptosis of VEGF-stimulated MKN-45 cells. Transwell matrix assays were used to measure migration and invasion, and WB assays were used to measure EMT. Results. LA inhibited the proliferation of SGC-7901, MKN-45, and MGC-803 cells and VEGF-stimulated MKN-45 cells. VEGFR-2 was identified as the target of LA. LA could also block cell cycle, induce apoptosis, and inhibit migration, invasion, and EMT of VEGF-stimulated MKN-45 cells. Functional analyses further revealed that the cytotoxic effect of LA on VEGF-stimulated MKN-45 cells potentially involved the PI3K/AKT and MEK/ERK signaling pathways. Conclusions. This study demonstrates that LA has anti-GC potency in vitro and in vivo. LA affects the proliferation, cycle, apoptosis, migration, invasion, and EMT by targeting VEGFR-2 and blocks the PI3K/AKT and MEK/ERK signaling pathways in VEGF-stimulated MKN-45 cells.