Synergistic anti-liver cancer effects of curcumin and total ginsenosides

查看全文 作　　者：Zhe [1]Deng;Xiao-Yan [2]Xu;Fenny [1]Yunita;Qing [3]Zhou;Yong-Rong [4]Wu;Yu-Xing [4]Hu;Zhi-Qi [5]Wang;Xue-Fei [2]Tian

机构地区：[1]Department of Internal Medicine,College of Integrated Chinese and Western Medicine,Hunan University of Chinese Medicine,Changsha 410208,Hunan Province,China;[2]Hunan Key Laboratory of Translational Research in Formulas and Zheng of Traditional Chinese Medicine,Hunan University of Chinese Medicine,Changsha 410208,Hunan Province,China;[3]The First Affiliated Hospital,Hunan University of Chinese Medicine,Changsha 410208,Hunan Province,China;[4]School of Basic Chinese Medical Sciences,Hunan University of Chinese Medicine,Changsha 410208,Hunan Province,China;[5]College of Pharmaceutical Sciences,Hunan University of Chinese Medicine,Changsha 410208,Hunan Province,China

出　　处：《World Journal of Gastrointestinal Oncology》索引2020年第12卷第10期,共13页

基　　金：the National Natural Science Foundation of China,No.81473617;the Science and Technology Department of Hunan Province,No.2017SK50310;the Hunan Education Department’s Science and Research Project,No.16K066. 摘　　要：BACKGROUND Liver cancer is the sixth most frequently occurring cancer in the world and the fourth most common cause of cancer mortality.The pathogenesis of liver cancer is closely associated with inflammation and immune response in the tumor microenvironment.New therapeutic agents for liver cancer,which can control inflammation and restore cellular immunity,are required.Curcumin(Cur)is a natural anti-inflammatory drug,and total ginsenosides(TG)are a commonly used immunoregulatory drug.Of note,both Cur and TG have been shown to exert anti-liver cancer effects.AIM To determine the synergistic immunomodulatory and anti-inflammatory effects of Cur combined with TG in a mouse model of subcutaneous liver cancer.METHODS A subcutaneous liver cancer model was established in BALB/c mice by a subcutaneous injection of hepatoma cell line.Animals were treated with Cur(200 mg/kg per day),TG(104 mg/kg per day or 520 mg/kg per day),the combination of Cur(200 mg/kg per day)and TG(104 mg/kg per day or 520 mg/kg per day),or 5-fluorouracil combined with cisplatin as a positive control for 21 d.Tumor volume was measured and the protein expression of programmed cell death 1 and programmed cell death 1 ligand 1(PD-L1),inflammatory indicators Toll like receptor 4(TLR4)and nuclear factor-κB(NF-κB),and vascular growth-related factors nitric oxide synthases(iNOS)and matrix metalloproteinase 9 were analyzed by Western blot analysis.CD4+CD25+Foxp3+regulatory T cells(Tregs)were counted by flow cytometry.RESULTS The combination therapy of Cur and TG significantly inhibited the growth of liver cancer,as compared to vehicle-treated animals,and TG showed dose dependence.Cur combined with TG-520 markedly decreased the protein expression of PD-L1(P<0.0001),while CD4+CD25+Foxp3+Tregs regulated by the PD-L1 signaling pathway exhibited a positive correlation with PD-L1.Cur combined with TG-520 also inhibited the cascade action mediated by NF-κB(P<0.0001),thus inhibiting the TLR4/NF-κB signalling pathway(P=0.0088,P<0.0001),which is associated with inflammation and acts on PD-L1.It also inhibited the NF-κB-MMP9 signalling pathway(P<0.0001),which is associated with tumor angiogenesis.CONCLUSION Cur combined with TG regulates immune escape through the PD-L1 pathway and inhibits liver cancer growth through NF-κB-mediated inflammation and angiogenesis. 关键词：Total ginsenosides CURCUMIN Liver cancer IMMUNE Inflammation Programmed cell death 1 ligand 1

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Synergistic anti-liver cancer effects of curcumin and total ginsenosides

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