板蓝根组酸对耐药人肝癌原位移植瘤的耐药逆转研究

THE STUDY OF ISATIS TINCTORIA L COMBINATION ACID REVERSING THE DRUG-RESISTANT OF TRANSPLANT TUMOR OF HUMAN HEPATOCELLULAR CARCINOMA IN SITU

目的 研究板蓝根组酸对耐药人肝癌原位移植瘤的耐药逆转作用及机制。方法 利用已建立的人耐药肝癌BEL - 74 0 4 /ADM动物模型 ,应用 FCM、HPL C和 RT- PCR等方法观察板蓝根组酸在体内对多药耐药逆转。结果 板蓝根组酸联合 ADM作用于耐药肝癌动物后 ,肿瘤体积和肿瘤重量分别为 0 .17± 0 .0 5 (cm3)、0 .73± 0 .19(g)明显小于 ADM组的 0 .5 8± 0 .13(cm3)、1.4 1± 0 .32 (g) ,两组间差异有显著性 (P<0 .0 5 ) ,肿瘤抑制率达 5 3%。其细胞内 ADM的含量 :板蓝根组酸 +ADM组为 1.0 7± 0 .0 7,ADM组为 0 .2 8± 0 .11,有显著性差异 (P<0 .0 1)。但 MDR1- m RNA,P- gp的表达改变不明显。结论 板蓝根组酸在体内能逆转耐药肝癌细胞对 ADM的耐药性 ,其逆转作用可能与降低 P- g P药物外排功能、增加细胞内药物浓度有关 。

Objective To study the roles and mechanisms of Isatis tinctoria L combination acid in transplanted tumor of human hepatocellular carcinoma in situ.Methods FCM,HPLC and RT-PCR were used to observe the reversing function of Isatis tinctoria L combination acid on hepatocellular carcinoma BEL-7404/ADM animal model,which is multi-drug-resistant model.Results The volume and weight of tumor were 0.17±0.05(cm 3)、0.73±0.19(g).The volume and weight of tumor in the group dealed with ADM were 0.58±0.13(cm 3)、1.41±0.32(g)(P<0.05).The rate of reversing was 53%.The concentration of ADM in the tumor cell were 1.07±0.07 and 0.28±0.11 in the group dealed with Isatis tinctorial combination acid and ADM respectively(P<0.01).The expression of MDR1-mRNA p-gp had no obvious changes.Conclusion Isatis tinctoria L combination acid could reverse the drug-resistant of hepatocellular carcinoma cell to ADM,which may be attributed to the decreasing of the drug excretion of p-gp and to increase the concentration of drug in cell,could be used as reversing drug in clinical test.