Effect of resveratrol and in combination with 5-FU on murine liver cancer.
Effect of resveratrol and in combination with 5-FU on murine liver cancer.
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DOI：
10.3748/wjg.v10.i20.3048
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发表时间：
2004-10
影响因子：
4.3
通讯作者：
Sheng-li Wu;Zhong-Jie Sun;Liang Yu;K. Meng;Xing-Lei Qin;C. Pan
中科院分区：
文献类型：
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作者：
Sheng-li Wu;Zhong-Jie Sun;Liang Yu;K. Meng;Xing-Lei Qin;C. Pan
目的研究白藜芦醇及其联合5-FU对小鼠肝癌的抗肿瘤作用。方法采用小鼠移植性肝癌模型，观察白藜芦醇(Res)单独或与5-FU合用的体内抗肿瘤活性。用流式细胞仪分析H22细胞周期。结果白藜芦醇10 mg/kg和15 mg/kg给H22荷瘤小鼠灌胃10d后，对小鼠肝癌H22的生长均有抑制作用，抑制率分别为36.3%(n=10)和49.3%(n=9)，与对照组(85+/-22vs68+/-17，P<；0.01)相比差异有统计学意义。白藜芦醇可诱导H22细胞发生S期阻滞，使细胞周期于S期的细胞比例由59.1%(n=9)增加到73.5%(n=9)，且呈剂量依赖关系(P<；0.05)。当5-FU与白藜芦醇10 mg/kg合用时，5-FU对荷瘤小鼠肿瘤生长的抑制作用也增强。20 mg/kg或10 mg/kg 5-FU联合10 mg/kg白藜芦醇与20 mg/kg或10 mg/kg 5-FU联合应用抑制率分别为77.4%和72.4%，其中5-FU单药抑制率分别为53.4%和43.8%(n=8)。联合用药组与5-FU组比较，差异有统计学意义。结论白藜芦醇可诱导H22细胞发生S时相阻滞，增强5-FU对小鼠肝癌22的抗肿瘤作用，并能明显拮抗其毒性。这些结果表明，白藜芦醇作为一种生化调节剂来增强5-FU的治疗效果，可能在肿瘤化疗中具有潜在的应用价值。
AIM To study the anti-tumor effect of resveratrol and in combination with 5-FU on murine liver cancer. METHODS Transplantable murine hepatoma22 model was used to evaluate the anti-tumor activity of resveratrol (RES) alone or in combination with 5-FU in vivo. H22 cell cycles were analyzed with flow cytometry. RESULTS Resveratrol could inhibit the growth of murine hepatoma22, after the mice bearing H22 tumor were treated with 10 mg/kg or 15 mg/kg resveratrol for ten days, and the inhibition rates were 36.3% (n = 10) and 49.3% (n = 9), respectively, which increased obviously compared with that in control group (85+/-22 vs 68+/-17, P<0.01). RES could induce the S phase arrest of H22 cells, and increase the percentage of cells in S phase from 59.1% (n = 9) to 73.5% (n = 9) in a dose-dependent manner (P<0.05). The enhanced inhibition of tumor growth by 5-FU was also observed in hepatoma22 bearing mice when 5-FU was administered in combination with 10 mg/kg resveratrol. The inhibition rates for 20 mg/kg or 10 mg/kg 5-FU in combination with 10 mg/kg resveratrol were 77.4% and 72.4%, respectively, compared with the group of 20 mg/kg or 10 mg/kg 5-FU alone, in which the inhibition rates were 53.4% and 43.8%, respectively (n = 8). There was a statistical significance between the combination group and 5-FU group. CONCLUSION RES could induce the S phase arrest of H22 cells and enhance the anti-tumor effect of 5-FU on murine hepatoma22 and antagonize its toxicity markedly. These results suggest that resveratrol, as a biochemical modulator to enhance the therapeutic effects of 5-FU, may be potentially useful in cancer chemotherapy.