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Synergistic effect of triptolide combined with 5-fluorouracil on colon carcinoma

Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China

Correspondence to:
Correspondence to:
Professor You-qing Zhu
Zhongnan Hospital of Wuhan University, Department of Gastroenterology, Zhongnan Hospital of Wuhan University, East-lake Road 169, Wuhan, Hubei province, P.R. China, 430071; uqingzhu{at}yahoo.com.cn;

Aim: 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.

Conclusion: 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.

Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BUN, blood urea nitrogen; CI, confidence interval; Cr, creatinine; DMSO, dimethyl sulfoxide; 5-FU, 5-fluorouracil; TPL, triptolide; TWHF, Tripterygium wilfordii Hook F