American ginseng berry enhances chemopreventive effect of 5-FU on human colorectal cancer cells
American ginseng berry enhances chemopreventive effect of 5-FU on human colorectal cancer cells
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DOI：
10.3892/or_00000521
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发表时间：
2009-10-01
期刊：
影响因子：
4.2
通讯作者：
Yuan, Chun-Su
中科院分区：
文献类型：
--
作者：
Li, Xiao-Li;Wang, Chong-Zhi;Yuan, Chun-Su
在这项研究中，我们研究了西洋参浆果提取物（AGBE）和5-氟尿嘧啶（5-FU）对人大肠癌细胞系SW-480，HCT-116和HT-29的可能的协同化学预防作用。采用高效液相色谱法测定西洋参中主要活性成分西洋参皂苷的含量。采用细胞计数法评价其抗增殖作用。AGBE（0.1- 1.0mg/ml）对SW-480、HCT-116和HT-29细胞生长有明显的抑制作用，且呈浓度依赖性。与单独应用5-FU或AGBE相比，5-FU和AGBE联合治疗的细胞生长下降更多，这表明AGBE可以减少达到预期效果所需的5-FU剂量，从而降低化疗药物的剂量相关毒性。细胞凋亡实验表明，AGBE在0.5和1.0mg/ml时可显著减少SW-480细胞的存活数，但不显著增加细胞凋亡。5-FU及5-FU与AGBE联合处理均未明显诱导细胞凋亡。细胞周期分析显示AGBE主要将SW-480细胞阻滞于G2/M期。5-FU使SW-480细胞处于S期的比例增加。联合用药组的实验结果表明，AGBE与5-FU单独用药相比，能显著增加5-FU对SW-480细胞S期的阻滞，并增加细胞G2/M期的分布。各处理组细胞周期蛋白A的增加趋势与S期和G2/M期细胞的增加趋势相似。AGBE对5-FU的协同作用机制可能是促进S期和G2/M期阻滞，而不是细胞凋亡。需要进一步的体内和临床试验来测试AGBE作为有价值的化学佐剂。
In this study, we investigated the possible synergistic chemopreventive effects of American ginseng berry extract (AGBE) and 5-fluorouracil (5-FU) on human colorectal cancer cell lines, SW-480, HCT-116 and HT-29. We used high-performance liquid chromatography to determine the contents of major ginsenosides, the active components of American ginseng, in AGBE. The antiproliferative effects were evaluated by the cell counting method. AGBE (0.1-1.0 mg/ml) significantly inhibited SW-480, HCT-116 and HT-29 cell growth in a concentration-dependent manner. Cell growth decreased more with the combined treatment of 5-FU and AGBE than with 5-FU or AGBE applied alone, suggesting that AGBE can reduce the dose of 5-FU needed to achieve desired effects and thereby decrease the dose-related toxicity of the chemotherapy agent. Cell apoptosis assay showed that AGBE markedly reduced the number of viable SW-480 cells at 0.5 and 1.0 mg/ml, but did not increase cell apoptosis significantly. Neither 5-FU nor co-treatment with 5-FU and AGBE induced cell apoptosis markedly. Cell cycle assay showed that AGBE mainly arrested SW-480 cells in the G2/M phase. 5-FU increased the percentage of SW-480 cells at the S phase of the cell cycle. The assay of combined treatment groups indicated that AGBE can heighten the arrest of SW-480 cells in the S phase induced by 5-FU, and increase the cell distribution in G2/M phase compared with 5-FU applied alone. The trend of increasing cyclin A was similar to the increase of S and G2/M phase cells in all treated groups. The enhancement of S and G2/M phase arrest, rather than cell apoptosis, should be the mechanism of synergistic effects of AGBE on 5-FU. Further in vivo and clinical trials are needed to test AGBE as a valuable chemo-adjuvant.