他莫昔芬联合化疗对胆管癌耐药细胞株QBC939／ADM的影响

目的探讨他莫昔芬（TAM）联合化疗对胆管癌耐药细胞株QBC939／ADM的影响及其机制。方法应用四甲基偶氮唑蓝比色法（MTT）检测TAM、多柔比星（ADM）、丝裂霉素（MMC）、长春地辛（VDS）及TAM分别联合其他三种化疗药对胆管癌细胞株QBC939及其耐药细胞株QBC939／ADM存活率的影响。流式细胞术（FCM）观察细胞生长周期及凋亡情况，观察细胞内ADM浓度的变化。免疫组织化学法（IHC）检测细胞P糖蛋白（P—gP）的表达。结果加用TAM后化疗药的作用得到增强，细胞凋亡率也明显提高。IHC结果显示QBC939／ADM呈过度表达，与QBC939相比，QBC939／ADM细胞内ADM的含量明显减少。用高浓度的TAM（10umol／L）作用QBC939／ADM后，细胞表面P—gP含量降低，细胞内ADM的含量相应提高。TAM对两种细胞的化疗都有增敏作用，其中耐药细胞的增敏作用更为显著。结论TAM可增强化疗药对胆管癌细胞株QBC939以及耐药细胞株QBC939／ADM的抑制作用，并可提高QBC939／ADM细胞内的药物浓度，其机制可能与其竞争结合过度表达的P—gp有关。

Significance of tamoxifen (TAM) in the combination chemotherapy of human multidrug-resistant bile duet carcinoma cell line

Objective To investigate the significance of tamoxifen in the combination chemotherapy of human multidrug-resistant bile duct carcinoma cell line (QBC939/ADM) and its mechanism. Methods The QBC939/AI)M was established, through exposure to gradually increased and the high and low alternated concentration of ADM persistently. The QBC939 and the QBC939/ADM were effected by single ADM, MMC, VDS or jointly with TAM. Drug sensitivity was measured by MTT. Growth cycle and apoptosis were performed by FCM. The level of their P-gp was detected by IHC. The content of ADM in the human cholangiocarcinoma cell line QBC939 was observed by FCM. Results The inhibitive rate of ADM, MMC, VDS to QBC939/ADM was rather lower than to QBC939. With the use of TAM, their chemotherapy effects were apparently enhanced and the apoptosis ratio increased comparably. The IHC results showed that the level of P-gp on the QBC939/ ADM was overexpressed, and the content of ADM in the QBC939/ADM group was much lower. Effected with the high content of TAM(10 μmol/L), the level of P-gp on the QBC939/ADM was decreased, with the content of ADM in the QBC939/ADM group increased comparably. TAM could both improve the chemotherapy effects of the two types of the cell, but the effect of the QBC939/ADM group was more apparent. Conclusion TAM can enhance the depressant effect of chemotherapy to both the two types of the cell, and increase the content of ADM in the QBC939/ADM group. TAM can be combined with the overexpressed P-gp.