Synergistic effects of beta-aescin and 5-fluorouracil in human hepatocellular carcinoma SMMC-7721 cells.
The effects and mechanisms of action of beta-aescin and 5-fluorouracil (5-FU), alone and in combination, were studied in human hepatocellular carcinoma SMMC-7721 cells. Growth inhibition, cell cycle distribution, apoptosis, Bcl-2 expression and caspase activity were assessed. The Isobole-method/interaction-index analysis was applied to evaluate the synergy, additivity or antagonism of these agents. The results indicate that mixtures of beta-aescin and 5-FU showed a synergistic effect on the 50% inhibitory effect when their ratio was 4:1 when compared with either agent alone. The mechanism of action could be through the synergistic arrest of the cell cycle, induction of apoptosis, activation of caspases-3, 8 and 9, and down-regulation Bcl-2 expression. The results suggest that mixtures of these two agents had a synergistic inhibitory effect on SMMC-7721 cells, an observation which might be useful for the further development of anti-cancer drugs.
Ming
Z J
ZJ
School of Pharmacy, College of Medicine, Soochow University, Suzhou 215123, PR China. mingzhijun@suda.edu.cn
Hu
Y
Y
Qiu
Y H
YH
Cao
L
L
Zhang
X G
XG
D031319:Aesculus / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D015536:Down-Regulation; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004928:Escin / Q000494:pharmacology / Q000627:therapeutic use*; D005472:Fluorouracil / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism
D000970:Antineoplastic Agents; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D004928:Escin; D020169:Caspases; D005472:Fluorouracil