Malik I A, Costea N V
Aga Khan University Hospital, Karachi, Pakistan.
Hematol Oncol. 1992 May-Aug;10(3-4):225-31. doi: 10.1002/hon.2900100314.
Verapamil has been shown to overcome acquired drug resistance to vincristine in P388 leukemia both in vitro and in vivo. To study the selectivity of this action, the effect of addition of verapamil on the cytotoxicity of vincristine was studied using lymphocytes from eight patients with chronic lymphocytic leukemia (CLL), lymphoblasts from a T-acute lymphoblastic leukemia (T-ALL) cell line (GM 3639), and peripheral blood lymphocytes (PBL) from eight normal healthy volunteers. Using the differential staining cytotoxicity (DiSC) assay, we demonstrated that verapamil at 1 microM concentration potentiated the in-vitro cytotoxicity of vincristine on CLL and GM 3639 cells in concentrations of 0.04-0.25 micrograms/l. There was however, no enhancement of cytotoxicity noted against the control PBL. The data demonstrate that verapamil preferentially enhances the in-vitro cytotoxicity of vincristine on CLL and GM 3639 cells but no enhancement of cytotoxicity is seen against PBL.
维拉帕米已被证明在体外和体内均可克服P388白血病对长春新碱产生的获得性耐药。为研究这种作用的选择性,使用来自8例慢性淋巴细胞白血病(CLL)患者的淋巴细胞、一株T急性淋巴细胞白血病(T-ALL)细胞系(GM 3639)的淋巴母细胞以及8名正常健康志愿者的外周血淋巴细胞(PBL),研究了添加维拉帕米对长春新碱细胞毒性的影响。使用鉴别染色细胞毒性(DiSC)测定法,我们证明1微摩尔浓度的维拉帕米可增强长春新碱对CLL细胞和GM 3639细胞的体外细胞毒性,长春新碱浓度为0.04 - 0.25微克/升。然而,未观察到对对照PBL的细胞毒性增强。数据表明,维拉帕米优先增强长春新碱对CLL细胞和GM 3639细胞的体外细胞毒性,但对PBL未观察到细胞毒性增强。