摘要
Shenmai injection(SMI)is a well-defined herbal preparation that is widely and clinically used as an adjuvant therapy for cancer.Previously,we found that SMI synergistically enhanced the activity of chemotherapy on colorectal cancer by promoting the distribution of drugs in xenograft tumors.However,the underlying mechanisms and bioactive constituents remained unknown.In the present work,the regulatory effects of SMI on tumor vasculature were determined,and the potential anti-angiogenic components targeting tumor endothelial cells(TECs)were identified.Multidimensional pharmacokinetic profiles of ginsenosides in plasma,subcutaneous tumors,and TECs were investigated.The results showed that the concentrations of protopanaxadiol-type(PPD)ginsenosides(Rb1,Rb2/Rb3,Rc,and Rd)in both plasma and tumors,were higher than those of protopanaxatriol-type(Rg1 and Re)and oleanane-type(Ro)ginsenosides.Among PPD-type ginsenosides,Rd exhibited the greatest concentrations in tumors and TECs after repeated injection.In vivo bioactivity results showed that Rd suppressed neovascularization in tumors,normalized the structure of tumor vessels,and improved the anti-tumor effect of 5-fluorouracil(5 FU)in xenograft mice.Furthermore,Rd inhibited the migration and tube formation capacity of endothelial cells in vitro.In conclusion,Rd may be an important active form to exert the anti-angiogenic effect on tumor after SMI treatment.
基金
supported by the China National Nature Science Foundation(81573496,81773989,81530098 and 81573494)
National Research Council of Science and Technology Major Project of China(2017ZX09201004-019 and 2019ZX09721001006-005)
International Science and Technology Center Program of China(2017YFE0109600)
Foundation for Innovative Research Groups of the National Natural Science Foundation of China(No.81421005)
Jiangsu Province Nature Science Foundation(No.BK20160076,China)
Jiangsu Province“333”project,China
Six talent peaks project in Jiangsu Province(YY-060),China
National Basic Research Program of China(973 Program,No.2017YFA0205400)
“Double First-Class”University project(CPU2018GF01,China)
作者简介
Corresponding authors:Xuequan Yao,Tel.:+862583271176,fax:+862583271060,E-mail addresses:34164236@qq.com;Corresponding authors:Guangji Wang,E-mail addresses:guangjiwang@hotmail.com;Corresponding authors:Fang Zhou,E-mail addresses:zf1113@163.com;These authors made equal contributions to this work:Chongjin Zhong;These authors made equal contributions to this work:Chao Jiang;These authors made equal contributions to this work:Suiying Ni
