体外短期化疗诱导Tca8113细胞株产生耐药性的研究

Induction of Multidrug Resistance in Tca8113 Cells by Transient Exposure to Different Chemotherapeutic Drugs

目的 探讨短期接触化疗药物后肿瘤细胞耐药性的产生情况及与化疗药物的关系。方法 将Tca8113细胞株在体外与化疗药物短期接触后 ,采用RT_PCR法检测其在mRNA水平上多药耐药基因 (MDR1)及多药耐药相关蛋白基因 (MRP)的表达情况 ,采用荧光分光光度计检测细胞内药物浓度的变化 ,以耐药的白血病细胞株K5 6 2 ADM作为对照。结果 化疗对敏感的Tca8113细胞株有明显的抑制作用 ,而对K5 6 2 ADM抑制作用不明显 ;Tca8113细胞株短期接触化疗药物后 ,在mRNA水平可检测到微量的MDR1和MRP的表达 ;耐药的K5 6 2 ADM细胞内药物浓度明显低于敏感的Tca8113细胞株。结论 耐药性的产生与MDR1和MRP表达水平密切相关。Tca8113细胞株短期接触化疗后即有微量的MDR1mRNA和MRPmRNA的表达 。

Objective\ The purpose of this study was to determine the effect of transient exposure to chemotherapeutic drugs on multidrug resistance of Tca8113 cells.Methods\ The MDR1 and MRP gene expressions in Tca8113 and K562/ADM cells lines were analyzed using reverse transcription polymerase chain reaction (RT_PCR), after the cells were treated with different cytotoxic drugs. The function and expressions of P_glycoprotein 170 and multidrug resistant associated protein were studied using fluorescence photometric assays.Results\ The inhibitive rate of Tca8113 cells was higher than that of K562/ADM, after exposure to chemotherapeutic drugs. The transient exposure to cytotoxic drugs weakly induced MDR1 and multidrug resistant associated protein expression in Tca8113 cells. The intracellular drug concentration in K562/ADM was lower than that in Tca8113 cells.Conclusion\ Induction of MDR1 and multidrug resistant associated protein gene expression response to cytotoxic drugs may be related with the increased multidrug resistance in drug_treated human tumor cells.\;