5-FU和黄芩苷在人类恶性上皮瘤细胞系中体外联合给药方案依赖性效应研究

Study on Schedule-dependent Synergism and Antagonism of the Combination of 5-FU and Baicalin in Human Carcinoma Cells in Vitro

关键词:  5-氟尿嘧啶  黄芩苷  给药方案依赖  等效线图解法  Chou-Talalay法

Key words:  5-FU  baicalin  schedule-dependent  isobologram  Chou-Talalay

摘要:

目的 对黄芩苷和5-FU在不同给药方案联合效应的依赖性进行研究。方法 通过体外人恶性肿瘤细胞系和正常细胞系的抗细胞增殖试验、细胞周期分布及凋亡试验，分别对应用黄芩苷和5-FU 3种联合方案(同时给药或序贯给药)进行效果评估。结果 等效线图解法和Chou-Talalay法的定性定量评估结果表明，相比同时给药方案，5-FU给药前给予适当剂量的黄芩苷不仅具有更显著的协同抗肿瘤活性，而且还可减小5-FU对正常细胞LO2的毒性。结论 黄芩苷和5-FU联合的协同和拮抗作用具有给药方案依赖性。机制可能是黄芩苷促进了5-FU的S期细胞周期捕获，以此限制了细胞通过细胞周期的能力。相反，对于5-FU后给予黄芩苷对肿瘤细胞系表现出拮抗效应，而正常细胞系表现出协同作用。

Abstract:

OBJECTIVE To investigate whether the addition of baicalin to 5-FU is able to increase their anti-tumor activity and to establish an effective schedule of combined treatment. METHODS The effects on cancer cell proliferation, cell cycle distribution, and apoptosis were evaluated in three different combination schedules (concomitant treatment, sequential treatment with baicalin followed by 5-FU, or 5-FU followed by baicalin) in a panel of human carcinoma and normal cells. RESULTS Isobologram and Chou-Talalay were respectively applied to qualitative and quantitative assessment of the drug combination. The results showed that compared with concomitant treatment, sequential treatment with baicalin followed by 5-FU not only increased the anti-tumor effects, but also reduced the toxicity to normal cells(LO2). CONCLUSION The combination of baicalin and 5-FU can provoke different synergism and antagonism depending on the treatment schedule. These effects are accompanied by the arrest of the surviving cells in the S phase, thus limiting their ability to proceed through the cell cycle. In contrast, the sequential treatment with 5-FU followed by baicalin can attenuate the effects.