甘草次酸-氟尿嘧啶复合物对人肝癌Bel-7402细胞的抗癌活性

Anticancer activity of glycyrrhetinic acid-fluorouracii compound in human hepatoma Be1~7402 celllines

【摘要】目的探讨甘草次酸-氟尿嘧啶类复合物-18β-甘草次酸酮-N-羟甲基-5-氟尿嘧啶（GA-Fu）的体外抗癌活性及细胞毒性。方法利用人肝癌多药耐药株Bel．7402细胞株，用MTT法观察GA—Fu对肝癌细胞增殖的抑制活性；用正常肝细胞changliver测定GA-Fu对正常细胞的毒性，并与5．氟尿嘧啶进行对照。结果GA—Fu与5-氟尿嘧啶（5-Fu）在浓度为25～250μg／ml范围内对人肝癌Bel-7402细胞具有明显的抑制活性，其抑制率随浓度提高而增强，呈浓度依赖性。尤其在较高浓度（200～250斗g／m1）下，GA—Fu对人肝癌Bel-7402细胞的增殖的抑制率（46％-57％）明显高于对照物5．氟尿嘧啶（33％～39％）（P〈0．05）；而对正常肝细胞的毒性（最高可达9．96％）则明显低于5-氟尿嘧啶（18．50％）（P〈0．05）。结论甘草次酸与抗癌药5-氟尿嘧啶进行耦合可提高5-氟尿嘧啶的抗癌活性并降低其对正常细胞的毒性，这可能是产生抗癌协同及化疗增敏作用的结果。本研究为甘草次酸-氟尿嘧啶类偶合物中筛选新型肝靶向抗癌候选药物奠定了一定基础。

Objective To investigate the in vitro anticancer activity of glycyrrhetinic acid-fluorou- racil compound （GA-Fu）. Methods The human Bel-7402 hepatoma cell lines were treated with GA-Fu compound, the cell proliferation capability was determined by methyl thiazolyl diphenyl-tetrazolium bromide （MTT） method. Normal chang liver cells were used to test its cytotoxicity. The data were compared with those of 5-fluorouracil （5-Fu） anticancer drug. Results Compound GA-Fu showed less cytotoxicity in chang liver normal cells （ lower than 5-Fu, P 〈 0. 05 ）. However, a significant inhibitory activity towards human Bel-7402 cancer cell proliferation, the inhibitory activity was higher than those of 5-Fu at all the con- centrations （ P 〈 0. 05）. Conclusions The combination of glycyrrhetinic acid with 5-Fuorouracil might in- crease its anticancer activity and decrease the cytotoxicity in notmal cells. It might produce synergic anti- cancer property and chemotherapy sensitizing effect. The results may provide an initial base for pharmaco- logical screening of new liver-targeting anticancer agent from glycyrrhetinic acid-fluorouracil compounds.