The isoflavone puerarin exerts anti-tumor activity in pancreatic ductal adenocarcinoma by suppressing mTOR-mediated glucose metabolism

科研成果详情

题名	The isoflavone puerarin exerts anti-tumor activity in pancreatic ductal adenocarcinoma by suppressing mTOR-mediated glucose metabolism
作者	Zhu, Hengyue 1,2; Xiao, Yanyi 1; Guo, Hangcheng1; Guo, Yangyang1; Huang, Youze 3; Shan, Yunfeng4; Bai, Yongheng1,5; Lin, Xiangyang2; Lu, Hong2
发表日期	2021-12-15
发表期刊	AGING-US 影响因子和分区
语种	英语
原始文献类型	Article
关键词	puerarin pancreatic ductal adenocarcinoma glucose metabolism apoptosis Akt/mTOR
其他关键词	CELL-PROLIFERATION ; CANCER ; INDUCTION ; SYSTEM
摘要	Puerarin (8-(beta-D-glucopyranosyl)-4 ', 7-dihydroxyisoflavone), a natural flavonoid compound isolated from the traditional Chinese herb Radix puerariae, have been demonstrated has potential anti-tumor effects via induction of apoptosis and inhibition of proliferation. However, the effect and molecular mechanism of puerarin in pancreatic ductal adenocarcinoma (PDAC) remains unknown. In this study, the tumor suppressive effects of puerarin were determined by both in-vitro and in-vivo assays. The effects of puerarin on the proliferation, apoptosis, migration and invasion of pancreatic cancer cells (PCCs), and tumor growth and metastasis in PDAC xenograft mouse model were performed. Puerarin treatment significantly repressed PCC proliferation. Puerarin induced the mitochondrial-dependent apoptosis of PCCs by causing a Bcl-2/Bax imbalance. Moreover, puerarin inhibited PCC migration and invasion by antagonizing epithelialmesenchymal transition (EMT). In nude mouse model, PDAC growth and metastasis were reduced by puerarin administration. Mechanistically, puerarin exerted its therapeutic effects on PDAC by suppressing Akt/mTOR signaling. Importantly, puerarin bound to the kinase domain of mTOR protein, affecting the activity of the surrounding amino acid residues associated with the binding of the ATP-Mg2+ complex. Further studies showed that the inhibitory effects of puerarin on PCCs were abolished by a mTOR activator, indicating a crucial role of mTOR in anti-tumor effects of puerarin in PDAC. As a result, puerarin hindered glucose uptake and metabolism by downregulating the oxygen consumption rate (OCR) and the extracellular acidification rate (ECAR) dependent upon HIF-1 alpha and glucose transporter GLUT1. Therefore, these findings indicated that puerarin has therapeutic potential for the treatment of PDAC by suppressing glucose uptake and metabolism via Akt/mTOR activity.
资助项目	Wenzhou Science and Technology Plan Project, China [Y20180100]; Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province [2018E10008]
出版者	IMPACT JOURNALS LLC
出版地	ORCHARD PARK
ISSN	1945-4589
卷号	13 期号:23 页码:25089-25105
页数	17
WOS类目	Cell Biology ; Geriatrics & Gerontology
WOS研究方向	Cell Biology ; Geriatrics & Gerontology
WOS记录号	WOS:000732027400014
收录类别	SCIE
PubMed ID	3486308
通讯作者地址	[Bai, Yongheng]Wenzhou Med Univ, Key Lab Diag & Treatment Severe Hepatopancreat Di, Affiliated Hosp 1, Wenzhou 325000, Peoples R China. ; [Lin, Xiangyang;Lu, Hong]Wenzhou Med Univ, Dept Lab Med, Affiliated Hosp 1, Wenzhou 325000, Peoples R China. ; [Bai, Yongheng]Wenzhou Med Univ, Ctr Hlth Assessment, Wenzhou 325000, Peoples R China.
引用统计	被引频次：1[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/15778
专题	第一临床医学院（信息与工程学院）、附属第一医院_浙江省胰脏肝脏危重性疾病重点实验室温州医科大学附属第一医院附属第一医院_检验科
通讯作者	Bai, Yongheng; Lin, Xiangyang; Lu, Hong
作者单位	1.Wenzhou Med Univ, Key Lab Diag & Treatment Severe Hepatopancreat Di, Affiliated Hosp 1, Wenzhou 325000, Peoples R China; 2.Wenzhou Med Univ, Dept Lab Med, Affiliated Hosp 1, Wenzhou 325000, Peoples R China; 3.Wenzhou Hosp Tradit Chinese Med, Dept Lab Med, Wenzhou 325000, Peoples R China; 4.Wenzhou Med Univ, Dept Hepatopancreatobiliary Surg, Affiliated Hosp 1, Wenzhou 325000, Peoples R China; 5.Wenzhou Med Univ, Ctr Hlth Assessment, Wenzhou 325000, Peoples R China
第一作者单位	第一临床医学院（信息与工程学院）、附属第一医院_浙江省胰脏肝脏危重性疾病重点实验室; 附属第一医院_检验科
通讯作者单位	第一临床医学院（信息与工程学院）、附属第一医院_浙江省胰脏肝脏危重性疾病重点实验室; 附属第一医院_检验科; 温州医科大学
第一作者的第一单位	第一临床医学院（信息与工程学院）、附属第一医院_浙江省胰脏肝脏危重性疾病重点实验室
推荐引用方式 GB/T 7714	Zhu, Hengyue,Xiao, Yanyi,Guo, Hangcheng,et al. The isoflavone puerarin exerts anti-tumor activity in pancreatic ductal adenocarcinoma by suppressing mTOR-mediated glucose metabolism[J]. AGING-US,2021,13(23):25089-25105.
APA	Zhu, Hengyue., Xiao, Yanyi., Guo, Hangcheng., Guo, Yangyang., Huang, Youze., ... & Lu, Hong. (2021). The isoflavone puerarin exerts anti-tumor activity in pancreatic ductal adenocarcinoma by suppressing mTOR-mediated glucose metabolism. AGING-US, 13(23), 25089-25105.
MLA	Zhu, Hengyue,et al."The isoflavone puerarin exerts anti-tumor activity in pancreatic ductal adenocarcinoma by suppressing mTOR-mediated glucose metabolism".AGING-US 13.23(2021):25089-25105.