Correction of altered plasma membrane potentials. A possible mechanism of cyclosporin A and verapamil reversal of pleiotropic drug resistance in neoplasia.
Correction of altered plasma membrane potentials. A possible mechanism of cyclosporin A and verapamil reversal of pleiotropic drug resistance in neoplasia.
复制标题
纠正改变的质膜电位。
DOI：
10.1007/bf00257315
复制
发表时间：
1988
影响因子：
3
通讯作者：
Gupta,S
中科院分区：
文献类型：
--
作者：
Vayuvegula,B;Slater,L;Meador,J;Gupta,S
我们最近发现，环孢菌素A（CsA）逆转多效性耐药的人急性淋巴细胞白血病在体外和柔红霉素耐药的埃里希腹水瘤在体内。在本研究中，我们研究了CsA可能逆转多效性耐药相对于细胞质膜电位和细胞内钙（[Ca 2 +]i）的变化的机制。用DIOC 5染料流式细胞仪测定膜电位，用Quin 2染料荧光分光光度法测定[Ca ~（2+）]水平。与相应的药物敏感亲本肿瘤相比，所有多效性（PDR）耐药肿瘤亚系的膜电位（膜去极化）均降低。相比之下，对照抗代谢物耐药急性白血病细胞系的膜电位不变。与亲本药物敏感细胞系相比，PDR亚系中[Ca 2 +] i的基础水平是可变的。所有PDR肿瘤亚系与CsA或维拉帕米孵育导致膜电位恢复到相应药物敏感亲本肿瘤的特征。环孢菌素A引起[Ca ~（2+）]i水平的变化。这些数据表明，膜电位的改变是恶性肿瘤的多效性耐药的机制之一，并表明这种改变是由CsA和维拉帕米纠正。
We have recently shown that cyclosporin A (CsA) reverses pleiotropic drug resistance in human acute lymphatic leukemia in vitro and daunorubicin resistance in Ehlrich ascites tumor in vivo. In the present study we examined the mechanisms by which CsA might reverse pleiotropic drug resistance relative to changes in cellular plasma membrane potentials and intracellular calcium ([Ca2+]i). Membrane potentials were measured with DIOC5 dye flowcytometrically and [Ca2+]ilevels with Quin 2 dye spectrofluorimetrically. All pleiotropic (PDR) drug-resistant tumor sublines had decreased membrane potentials (membrane depolarized) compared with their corresponding drug-sensitive parental tumors. In comparison, the membrane potentials of a control antimetaboliteresistant acute leukemia cell line were unchanged. The basal levels of [Ca2+]iin the PDR sublines were variable compared with those of parental drug-sensitive cell lines. Incubation of all PDR tumor sublines with CsA or verapamil resulted in the restoration of membrane potentials to that characteristic of the corresponding drug-sensitive parental tumor. Cyclosporin A produced variable changes in the levels of [Ca2+]i. These data suggest that alteration of membrane potentials is one of the mechanisms responsible for pleiotropic drug resistance in malignancy and show that this alteration is corrected by CsA and verapamil.