阿霉素细胞水平药物动力学在维拉帕米对Swis－3T3细胞的化学增敏效应中不起作用

Doxorubicin cellular pharmacokinetics plays no role in chemosensitizing effect of verapamil on Swiss 3T3 cells

阿霉素细胞水平药物动力学在维拉帕米对Ｓｗｉｓ３Ｔ３细胞的化学增敏效应中不起作用王楠，汤仲明，章扬培，丁清明（北京放射医学研究所，北京１００８５０，中国）关键词阿霉素；维拉帕米；抗药性；药物动力学；成纤维细胞；培养的肿瘤细胞目的：确定维拉帕米（Ｖｅｒ...

AIM: To find whether or not the doxorubicin (Dox) cellular pharmacokinetics plays a role in chemosensitizing effect of verapamil (Ver) on drug sensitive cells. METHODS: Cytotoxicity and cellular Dox contents (during accumulation and retention periods) were measured in the absence and presence of verapamil in Swiss 3T3 cells and compared with those in multidrug resistant (MDR) MCF 7 Adr cells and drug sensitive MCF 7 WT cells. mdr 1 mRNA expression in Swiss 3T3 cells was analyzed. RESULT: Dox cytotoxicity was enhanced 2 0 fold in Swiss 3T3 cells by Ver (3 μmol·L -1 ) and 3 6 fold in MCF 7 Adr cells by Ver (6 μmol·L -1 ) , but not in MCF 7 WT cells (Ver 6 μmol·L -1 ). Cellular accumulation of equi effective concentrations of Dox increased at 6 h incubation in the presence of Ver in Swiss 3T3 (1 5 fold) and MCF 7 WT cells (2 1 fold) but decreased rapidly in MCF 7 Adr cells by 20 % to 50 % compared to that in the absence of Ver. Cellular retention of Dox decreased after 10 min increase in the presence of Ver in Swiss 3T3 cells compared to that in the absence of Ver, that was similar to that in MCF 7 WT cells, while the retention was augmented by Ver in MCF 7 Adr cells. Slot blot analysis of RNA revealed no mdr 1 gene expression in Swiss 3T3 cells. CONCLUSION: Changes in cellular accumulation and retention of Dox did not account for the chemosensitizing effect of Ver on Swiss 3T3 cells.