机构：[1]Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China.[2]Department of Dermatology, The Affiliated Hospital of Southwest Medical University, Luzhou, China.[3]The Public Platform of Advanced Detecting Instruments, Public Center of Experimental Technology, Southwest Medical University, Luzhou, China.[4]Human Microecology and Precision Diagnosis and Treatment of Luzhou Key Laboratory, Luzhou, China.[5]Cardiovascular and Metabolic Diseases of Sichuan Key Laboratory, Luzhou, China.[6]Institute of Drug Metabolism and Pharmaceutical Analysis, Zhejiang University, Hangzhou, China.
Sanguinarine (SAG) is the most abundant constituent of Macleaya cordata (Willd.) R. Br. (Popaceae). SAG has shown antimammary and colorectal metastatic effects in mice in vivo, suggesting its potential for cancer chemotherapy.To determine the antimetastatic effect and underlying molecular mechanisms of SAG on melanoma.CCK8 assay was used to determine the inhibition of SAG on the proliferation of A375 and A2058 cells. Network pharmacology analysis was applied to construct a compound-target network and select potential therapeutic targets of SAG against melanoma. Molecular docking simulation was conducted for further analysis of the selected targets. In vitro migration/invasion/western blot assay with 1, 1.5, 2 μM SAG and in vivo effect of 2, 4, 8 mg/kg SAG in xenotransplantation model in nude mice.The key targets of SAG treatment for melanoma were mainly enriched in PI3K-AKT pathway, and the binding energy of SAG to PI3K, AKT, and mTOR were -6.33, -6.31, and -6.07 kcal/mol, respectively. SAG treatment inhibited the proliferation, migration, and invasion ability of A375 and A2058 cells (p < 0.05) with IC50 values of 2.378 μM and 2.719 μM, respectively. It also decreased the phosphorylation levels of FAK, PI3K, AKT, mTOR and protein expression levels of MMP2 and ICAM-2. In the nude mouse xenograft model, 2, 4, 8 mg/kg SAG was shown to be effective in inhibiting tumour growth.Our research offered a theoretical foundation for the clinical antitumor properties of SAG, further suggesting its potential application in the clinic.
基金：
National Natural Science
Foundation (81672458, 82003850), the Grants from the Science and
Technology Planning Project of Sichuan Province (2021JDTD0003,
2022NSFSC0576，2022YFS0631，2022YFS0626, 2022YFS0625), the
Sichuan Province Post Doctoral Fund Special Assistance Program
(202027)，the Science and Technology Cooperation Project of Gulin
County People’s and Hospital and Southwest Medical University
Affiliated Hospital (2022GLXNYDFY12)，Suining First People’s
Hospital Southwest Medical University Cooperation Project
(2022SNXNYD02), Office of science & technology and talent work
of Luzhou (2022-JYJ-138) and the Youth Program of Southwest
Medical University (2021ZKQN098).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2023]版：
大类|3 区医学
小类|2 区医学实验技术2 区药学2 区植物科学
最新[2023]版：
大类|3 区医学
小类|2 区医学实验技术2 区药学2 区植物科学
第一作者：
第一作者机构：[1]Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China.[2]Department of Dermatology, The Affiliated Hospital of Southwest Medical University, Luzhou, China.[3]The Public Platform of Advanced Detecting Instruments, Public Center of Experimental Technology, Southwest Medical University, Luzhou, China.[4]Human Microecology and Precision Diagnosis and Treatment of Luzhou Key Laboratory, Luzhou, China.[5]Cardiovascular and Metabolic Diseases of Sichuan Key Laboratory, Luzhou, China.[6]Institute of Drug Metabolism and Pharmaceutical Analysis, Zhejiang University, Hangzhou, China.
共同第一作者：
通讯作者：
通讯机构：[1]Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China.[3]The Public Platform of Advanced Detecting Instruments, Public Center of Experimental Technology, Southwest Medical University, Luzhou, China.[4]Human Microecology and Precision Diagnosis and Treatment of Luzhou Key Laboratory, Luzhou, China.[5]Cardiovascular and Metabolic Diseases of Sichuan Key Laboratory, Luzhou, China.[*1]Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China[*2]The Public Platform of Advanced Detecting Instruments, Public Center of Experimental Technology, Southwest Medical University, Luzhou, China[*3]Human Microecology and Precision Diagnosis and Treatment of Luzhou Key Laboratory, Luzhou, China[*4]Cardiovascular and Metabolic Diseases of Sichuan Key Laboratory, Luzhou, China
推荐引用方式(GB/T 7714)：
Qi Xiaoyi,Chen Yonglan,Liu Sha,et al.Sanguinarine inhibits melanoma invasion and migration by targeting the FAK/PI3K/AKT/mTOR signalling pathway[J].Pharmaceutical biology.2023,61(1):696-709.doi:10.1080/13880209.2023.2200787.
APA：
Qi Xiaoyi,Chen Yonglan,Liu Sha,Liu Li,Yu Zehui...&Muhan L€.(2023).Sanguinarine inhibits melanoma invasion and migration by targeting the FAK/PI3K/AKT/mTOR signalling pathway.Pharmaceutical biology,61,(1)
MLA：
Qi Xiaoyi,et al."Sanguinarine inhibits melanoma invasion and migration by targeting the FAK/PI3K/AKT/mTOR signalling pathway".Pharmaceutical biology 61..1(2023):696-709
