人食管癌细胞抗药机制的探讨

Mechanism of human esophageal cancer cell resistance to drugs

目的 :在建立体外多药抗药细胞株的基础上 ,研究其抗药性形成机制 ,寻求克服抗药性的方法。方法 :用人食管癌上皮细胞Eca 10 9细胞 ,在无诱导剂的情况下 ,以递加培养液中阿霉素 (ADM)质量浓度的方法 ,建立了Eca 10 9/ADM多药抗药细胞株。用荧光光度法测定抗药细胞内还原性谷胱甘肽 (GSH)含量及ADM的累积量。结果 :研究发现Eca 10 9/ADM细胞内GSH含量增加、降低细胞内GSH的含量 ,细胞的抗药性呈现部分逆转 ;抗药细胞内ADM的质量浓度较敏感株Eca 10 9细胞低 ,用维拉帕米能增加抗药细胞内ADM的质量浓度 ,同时部分逆转其抗药性。结论 :Eca 10

Aim: In order to investigate the mechanism of multidrug resistance in Eca 109/ADM cell line and find ways to reverse resistance to drugs.Methods: Using a multidrug resistant cell line of Eca 109/ADM established by stepwise selection on exposure to increasing dose of Adriamycin(ADM) in the absence of mutagenic agents,GSH content and ADM accumulation in cells were determined. Results: GSH content in Eca 109 and Eca 109/ADM cells are (0.32±0.05),(0.69±0.09)ng/10 6 cells respectively.At lowering intracellular GSH content,the drug resistance was only overcome partially.Intracellular ADM accumulation in Eca 109/ADM cells was lower than that in Eca 109 cell.Verapamil in combination with ADM was found to enhance intracellular ADM accumulation in Eca 109/ADM cells and brought about the reversion of drug resistance. Conclusion:The mechanism of Eca 109/ADM cell resistance to multiple drug results mainly from increased GSH content and decreased the drug accumulation in cells.