Synergistic Inhibitory Effect of Traditional Chinese Medicine Astragaloside IV and Curcumin on Tumor Growth and Angiogenesis in an Orthotopic Nude-Mouse Model of Human Hepatocellular Carcinoma.
The aim of the present study was to investigate the efficacy of the traditional Chinese medicine (TCM), astragaloside IV (AS-IV) and curcumin on tumor growth and angiogenesis in an orthotopic nude-mouse model of human hepatocellular carcinoma (HCC). We have previously shown the usefulness of orthotopic models of human cancer for evaluation of the efficacy of TCM.



Nude mice with orthotopic HepG2 HCC were treated with vehicle control (0.01 ml/g normal saline), cisplatinum (2 mg/kg), AS-IV (20 mg/kg), curcumin (100 mg/kg) or AS-IV plus curcumin (20 mg/kg + 100 mg/kg). Tumor inhibition in each group was evaluated by tumor weight at autopsy. The effect of AS-IV and curcumin on tumor angiogenesis was assessed by CD34 staining and expression of fibroblast growth factor-2 (FGF2), matrix metalloproteinase 2 (MMP2), vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), thrombosis-related factor tissue factor (TF) and coagulation factor VII (FVII), as well as microRNAs miR-122 and miR-221.



AS-IV and curcumin alone and in combination significantly reduced mean tumor weight compared to vehicle control (p<0.05). Tumor microvessel count was reduced by AS-IV and curcumin alone. Expression of FGF2, MMP2, VEGF, HGF, TF and FVII was reduced by AS-IV and curcumin alone. AS-IV and curcumin alone up-regulated expression of miR-122 and down-regulated that of miR-221. The combination of AS-IV and curcumin demonstrated significant synergistic effects on microvessel count as well as on expression of angiogenic and thrombosis-related factors and microRNAs.



The present study indicates future clinical potential of combination therapy with AS-IV and curcumin for HCC.
Department of Chinese Medicine, School of Basic Medical Sciences, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, P.R. China.
Shuo
S
Zhang
Department of Chinese Medicine, School of Basic Medical Sciences, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, P.R. China talknow@163.com all@anticancer.com.
Decai
D
Tang
Department of Clinical Chinese Pharmacy, Nanyang Institute of Technology, Nanyang, Henan, P.R. China.
Wenhua
W
Zang
Department of Chinese Medicine, School of Basic Medical Sciences, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, P.R. China.
Gang
G
Yin
Department of Pathology, School of Basic Medical Sciences, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, P.R. China.
Jianguo
J
Dai
Origin Biosciences Inc., Nanjing, Jiangsu, P.R. China.
Y U
YU
Sun
AntiCancer, Inc., San Diego, CA, U.S.A.|Origin Biosciences Inc., Nanjing, Jiangsu, P.R. China.
Zhijian
Z
Yang
AntiCancer, Inc., San Diego, CA, U.S.A. talknow@163.com all@anticancer.com.
Robert M
RM
Hoffman
Department of Chinese Medicine, School of Basic Medical Sciences, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, P.R. China.
Xiuxia
X
Guo
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D048708:Cell Growth Processes / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D015536:Down-Regulation; D004357:Drug Synergism; D056945:Hep G2 Cells; D064593:Heterografts; D006801:Humans; D008113:Liver Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D011897:Random Allocation; D012503:Saponins / Q000008:administration & dosage / Q000494:pharmacology*; D014315:Triterpenes / Q000008:administration & dosage / Q000494:pharmacology*
D012503:Saponins; D014315:Triterpenes; C052064:astragaloside A; D003474:Curcumin
Astragaloside IV; TCM; angiogenesis; curcumin; hepatocellular carcinoma; microRNA; nude mouse; orthotopic