Synergistic effect of 5-fluorouracil with gambogic acid on BGC-823 human gastric carcinoma.
The design of novel targeted or combination therapies may improve treatment options for gastric cancer. In this study, we determined the inhibitory effects of 5-fluorouracil (5-FU) combined with gambogic acid (GA) on BGC-823 human gastric carcinoma cells in vitro and in vivo and investigated the underlying mechanisms. 5-FU combined with GA inhibited the viability of BGC-823 human gastric cells in a concentration-dependent manner. The pro-apoptotic activity of the two-drug combination was much stronger than single. Furthermore, the results showed GA could regulate the metabolic enzymes of 5-FU. GA decreased the mRNA levels of thymidine synthetase (TS) and dihydropyrimidine dehydrogenase (DPD), while increased the mRNA level of orotate phosphoribosyltransferase (OPRT). Moreover, combined treatment caused significantly growth inhibition of human tumor xenografts in vivo. Taken together, our data showed that GA attenuated 5-FU-induced apoptosis by modulating metabolic enzymes of 5-FU and the antigastric cancer effect of two drugs combination was much stronger than that of GA or 5-FU alone.
Wang
Jun
J
Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, China.
Liu
Wei
W
Zhao
Qing
Q
Qi
Qi
Q
Lu
Na
N
Yang
Yong
Y
Nei
Fei-Fei
FF
Rong
Jing-Jing
JJ
You
Qi-Dong
QD
Guo
Qing-Long
QL
D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004357:Drug Synergism; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D044004:Xanthones / Q000494:pharmacology*
D017304:Annexin A5; D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; D012333:RNA, Messenger; D044004:Xanthones; C052659:gambogic acid; D005472:Fluorouracil