板蓝根活性成分对肝癌耐药细胞耐药性的逆转作用研究

THE REVERSE ROLE OF THE ACTIVITY OF BANLANGEN TO HUMAN MULTIDRUG-RESISTANT HEPATOCARCINOMA CELL

目的 研究板蓝根提取物对人肝癌耐药细胞株BEL - 74 0 4 /ADM耐药逆转作用及其逆转机制。方法 用人肝癌细胞株BEL - 74 0 4 /ADM筛选出板蓝根活性单体 ,进行耐药逆转试验 ;使用高效液相色谱仪 (HPLCA)测定细胞内药物含量 ,来探讨其逆转机制。结果 (1)板蓝根活性单体 5b在高浓度 (>5 0 0 μg/ml)时对亲本细胞及耐药细胞均有细胞毒作用 ,抑制率大于 5 0 % ,在非细胞毒剂量 (<2 5 0 μg/ml)与阿霉素合用后能逆转BEL - 74 0 4 /ADM对阿霉素的耐药性 ,逆转倍数为 2～ 6倍 ;(2 )阿霉素与 5b合用时细胞内阿霉素含量较单独应用时明显升高 (P <0 0 0 1) ,分别为 5 6 .875± 9 349pg和 19 6 2 5± 0 .6 2 9pg。 结论 板蓝根活性单体 5b在非细胞毒剂量范围内能逆转BEL - 74 0 4 /ADM对阿霉素的耐药性 ,其逆转作用可能与降低 p - gp药物外排功能。

Objective To study the reverse role and mechanisms of the activity of BanLanGen to human multidrug-resistant hepatocarcinoma cell BEL-7404/ADM.Methods The active monomers of BanLanGen was selected and their reverse role to multidrug-resistance was detected with MTT method.The content of ADM in cells was determined with high performance liquid chromatography (HPLCA).Results An active monomers of BanLanGen 5b selected with this model had cytotoxic role to BEL-7404 and BEL-7404/ADM in high concentration(>500μg/ml),whereas reverse role to ADM for BEL-7404/ADM in noncytotoxic concentration (<250μg/ml),which reverse times were 2～6.The ADM accumulation in BEL-7404 cells increased significantly(P<0.001) when ADM coupled with 5b than that used only,56.875±9.349 pg,19.625±0.629 pg,respectively.Conclusion The active monomers of BanLanGen 5b can reverse resistance of BEL-7404/ADM,and the reverse role may be related with intracellular anticancer agents content increase.