Synergistic effect of triptolide combined with 5-fluorouracil on colon carcinoma.
OBJECTIVE
To investigate the inhibitive effects of triptolide (TPL) combined with 5-fluorouracil (5-FU) on colon carcinoma HT-29 cells in vitro and in vivo and their side effects.


METHODS
HT-29 cells were cultured with RPMI 1640 medium. The single or combined effects of TPL and 5-FU on HT-29 cells were examined by MTT assay, flow cytometry. The combined effects were evaluated by the median-effect principle. The model of tumour xenografts was established in nude mice. TPL 0.25 mg/kg/day and 5-FU 12 mg/kg/day, either in combination or on their own, were injected into mice and the inhibitive effects and side effects were observed.


RESULTS
TPL and 5-FU either combined or alone inhibited significantly the proliferation of HT-29 cells and induced obvious apoptosis. Mean (SD) growth inhibition rate reached 94.92 (2.76)% and the apoptic rate at 48 h reached 41.71 (1.38)%. The combined effects were synergistic (CI<1) at lower concentrations. TPL or 5-FU alone inhibited significantly the growth of tumour xenografts and the inhibition rates were 78.53% and 84.16%; the drugs combined had more significant effect, the tumour inhibition rate reaching 96.78%. During the course of chemotherapy, no obvious side effect was observed.


CONCLUSIONS
The combined effects of TPL and 5-FU on the growth of colon carcinoma in vitro and in vivo were superior to the effects when the agents were used individually. TPL combined with 5-FU had synergistic effects at lower concentrations and promoted apoptosis, but did not increase the side effects of chemotherapy.
Tang
Xiao-yan
XY
Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei province, China.
Zhu
You-qing
YQ
Tao
Wen-hui
WH
Wei
Bai
B
Lin
Xiao-ling
XL
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002277:Carcinoma / Q000473:pathology*; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology*; D004224:Diterpenes / Q000008:administration & dosage / Q000494:pharmacology*; D004357:Drug Synergism; D004852:Epoxy Compounds / Q000008:administration & dosage / Q000494:pharmacology; D005472:Fluorouracil / Q000008:administration & dosage / Q000494:pharmacology*; D019073:HT29 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010616:Phenanthrenes / Q000008:administration & dosage / Q000494:pharmacology*; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D029757:Tripterygium; D023041:Xenograft Model Antitumor Assays
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000964:Antimetabolites, Antineoplastic; D004224:Diterpenes; D004852:Epoxy Compounds; D010616:Phenanthrenes; D010936:Plant Extracts; C001899:triptolide; D005472:Fluorouracil