人膀胱癌多重抗药性逆转的实验研究

为探讨膀胱癌多重抗药性逆转机理，应用阿霉素（ＡＤＭ）大剂量短暂冲击结合低浓度持续递增法，获得了具有多重抗药性的ＢＩＵ８７Ｒ／ＡＤＭ细胞。通过测定细胞内ＡＤＭ聚积量和钙离子浓度，发现ＢＩＵ８７Ｒ／ＡＤＭ细胞内ＡＤＭ聚积量显著低于ＢＩＵ８７细胞（Ｐ＜００５）；维拉帕米（ＶＰＬ）、奎宁能使ＢＩＵ８７Ｒ／ＡＤＭ细胞内ＡＤＭ聚积量增加（Ｐ＜００５），两者协同应用基本上可逆转ＢＩＵ８７Ｒ／ＡＤＭ细胞的抗药性。结果表明：（１）细胞内ＡＤＭ聚积量减少是抗药细胞的重要变化，在细胞抗药性发生机理中可能起主导作用，（２）ＶＰＬ、奎宁能逆转ＢＩＵ８７Ｒ／ＡＤＭ细胞的抗药性，可能与增加细胞内ＡＤＭ聚积量有关，与钙通道无关。

experimental investigations on the reversal of multidrug resistance in a human bladder transitional carcinoma cell line

A doxourubicin (ADM) resistant human bladder transitional cell carcinoma cell line, BIU 87R/ADM,has been established in vitro by impulsive exposing of BIU 87R parent cells in a single high concentration of ADM followed by progressively higher concentrations.It was found that ADM content in BIU 87R/ADM cells was significantly lower than that of BIU 87 ( P <0 05)and verapamil and/or quinine could significantly increse the ADM accumulation in BIU 87R/ADM cells (P<0 05). The ADM resistance could be almost completely reversed by the use of verapamil and quinine. These findings suggested that (1) Decrease in drug accumulation was an important phenomenum in BIU 87R/ADM, playing an important role in the mechanism of MDR resistance. (2) It was not the effect on calcium channels while intracellular ADM accumulation would restore the drug sensitivity of BIU 87R/ADM in the presence of verapamil and quinine.