六氢姜黄素增强 5-氟尿嘧啶对 HT-29 人结肠癌细胞的抑制作用。
Hexahydrocurcumin enhances inhibitory effect of 5-fluorouracil on HT-29 human colon cancer cells.
机构信息
Department of Anatomy, Faculty of Medical Science, Naresuan University, Phitsanulok 65000, Thailand.
出版信息
World J Gastroenterol. 2012 May 21;18(19):2383-9. doi: 10.3748/wjg.v18.i19.2383.
AIM
To investigate the ability of hexahydrocurcumin (HHC) to enhance 5-fluorouracil (5-FU) in inhibiting the growth of HT-29 cells by focusing on cyclooxygenase (COX)-2 expression.
METHODS
Antiproliferative effects of HHC and 5-FU, alone and in combination, on growth of HT-29 human colon cancer cells were assessed using 5-diphenyltetrazolium bromide (MTT) reduction assay. In combination treatment, low doses of 5-FU were used combined with various concentrations of HHC to minimize the toxicity and side effects of 5-FU. The therapeutic effects of these drugs on down-regulation of COX-2 mRNA and protein expression were examined using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting analysis.
RESULTS
MTT reduction assay indicated that HHC alone markedly decreased the viability of HT-29 human colon cancer cells compared to control. Semi-quantitative RT-PCR analysis indicated that HHC is a selective COX-2 inhibitor. This finding was supported by the observation that HHC significantly down-regulates COX-2 mRNA expression compared to the control (control: 100.05% ± 0.03% vs HHC: 61.01% ± 0.35%, P < 0.05) but does not alter COX-1 mRNA. In combined treatment, addition of HHC to a low dose of 5-FU exerts a synergistic effect against the growth of HT-29 cells by markedly reducing cell viability to a greater degree than monotherapy. Semi-quantitative RT-PCR indicated that 5-FU at the concentration of 5 μmol/L in combination with HHC at the concentration of 25 μmol/L significantly down-regulates COX-2 mRNA expression when compared with values in cells treated with 5-FU or HHC alone (HHC + 5-FU: 31.93% ± 5.69%, 5-FU: 100.66% ± 4.52% vs HHC: 61.01% ± 0.35%, P < 0.05).
CONCLUSION
HHC together with 5-FU exerts a synergistic effect and may prove chemotherapeutically useful in treating human colon cancer.
目的
通过研究十六氢姜黄素（HHC）对环氧合酶（COX）-2表达的抑制作用，探讨其增强 5-氟尿嘧啶（5-FU）抑制 HT-29 细胞生长的能力。
方法
采用 5-二苯基四氮唑溴盐（MTT）还原法检测 HHC 和 5-FU 单独及联合应用对 HT-29 人结肠癌细胞生长的抑制作用。在联合治疗中，采用低剂量 5-FU 与不同浓度 HHC 联合应用，以最大限度地减少 5-FU 的毒性和副作用。采用半定量逆转录-聚合酶链反应（RT-PCR）和 Western 印迹分析检测这些药物对 COX-2 mRNA 和蛋白表达下调的治疗作用。
结果
MTT 还原试验表明，与对照组相比，HHC 单独处理明显降低 HT-29 人结肠癌细胞的活力。半定量 RT-PCR 分析表明，HHC 是一种选择性 COX-2 抑制剂。这一发现得到了以下观察结果的支持：与对照组（对照组：100.05%±0.03%vs HHC：61.01%±0.35%，P<0.05）相比，HHC 显著下调 COX-2 mRNA 表达，但不改变 COX-1 mRNA。在联合治疗中，HHC 与低剂量 5-FU 联合应用对 HT-29 细胞的生长具有协同作用，与单药治疗相比，细胞活力显著降低。半定量 RT-PCR 表明，与单独用 5-FU 或 HHC 处理的细胞相比，浓度为 5μmol/L 的 5-FU 与浓度为 25μmol/L 的 HHC 联合应用时，显著下调 COX-2 mRNA 表达（HHC+5-FU：31.93%±5.69%，5-FU：100.66%±4.52%vs HHC：61.01%±0.35%，P<0.05）。
结论
HHC 与 5-FU 联合应用具有协同作用，可能在治疗人结肠癌方面具有化疗应用价值。
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