黄芩素对卵巢癌耐药细胞株A2780/ADM逆转作用实验研究

目的探讨黄芩素对卵巢癌耐药细胞株A2780/ADM耐药逆转作用及机制.方法MTT法观察药物对细胞的生长抑制作用;免疫组化法检测细胞P-糖蛋白(P-Gp)和多药耐药相关蛋白(MRP)的表达;采用高效液相色谱法(HPLC)测定细胞内ADM的浓度.结果卵巢癌耐药细胞株A2780/ADM对多种化疗药物产生多药耐药性,耐药细胞P-Gp和MRP的阳性率显著高于亲本细胞(P＜0.01);黄芩素在非细胞毒剂量时与ADM合用后能逆转A2780/ADM对ADM的耐药性;ADM与黄芩素合用时,其细胞内ADM的含量较单独使用明显增高.结论卵巢癌耐药细胞株A2780/ADM对多种化疗药物具有多药耐药性,其多药耐药性与P-Gp和MRP过量表达有关;黄芩素在非细胞毒剂量时能逆转A2780/ADM对ADM的耐药性,其逆转作用可能与降低P-Gp药物外排功能、增加细胞内药物浓度有关.

A study of the reverse effect of scutellarein on multidrug-resistant human ovarian carcinoma cell line A2780/ADM

Objective To study the reverse roles of reverse effect of Scutellarein on multidrug-resistant human ovarian carcinoma cell line A2780/ADM. Methods A2780/ADM sensitivity to multianticancer agent was evaluated by MTT assay. The expressions of P-Gp and MRP were detected by immunohistochemical method. The content of ADM in cells was determined with high performance liquid chromatography (HPLC). Results The human ovarian carcinoma cell line A2780/ADM showed drug resistance to multianticancer agent. The expressions of P-Gp and MRP in A2780/ADM were significantly higher than in A2780 ( P <0.01). Scutellarein in noncytotoxic concentration had reverse effect to ADM,so when ADM coupled with the Scutellarein,the ADM accumulation in cells increased significantly than used only. ( P <0.01) Conclusion A2780/ADM cells is a multidrug resistant model of human ovarian carcinoma which multidrug resistance is related with over-expression of P-Gp and MRP. Scutellarein can reverse the resistance of A2780/ADM,and this reverse effect may be related with the increase of intracellular anticancer agents concentration.