Kubota M, Kataoka A, Okuda A, Bessho R, Lin Y W, Wakazono Y, Usami I, Akiyama Y, Furusho K
Department of Pediatrics, Faculty of Medicine, Kyoto University, Japan.
Biochem Biophys Res Commun. 1995 Aug 15;213(2):541-9. doi: 10.1006/bbrc.1995.2165.
We have selected calcium ionophore (A23187)-resistant cells (AR-7) in a human promyelocytic leukemia cell line, HL-60. AR-7 showed approximately 8.5-fold resistance to A23187 compared with the wild type cells after continuous exposure for 3 days. AR-7 had cross resistance to ionomycin (4.6-fold) and thapsigargin (340-fold) which can also increase intracellular Ca++. Similar magnitude of resistance to apoptosis, as defined by characteristic morphology and internucleosomal DNA fragmentation, induced by these agents was observed after 4 hr of incubation. However, both the elevation of intracellular Ca++ following stimulation with various concentrations of A23187 and the sensitivity to anti-cancer agents including etoposide, 1-beta-D arabinofuranosylcytosine, and hydroxyurea were comparable between the two cell types. This cell line is considered to be useful for exploring the mechanism(s) of cell death, especially apoptosis, induced by calcium ionophore.
我们已在人早幼粒细胞白血病细胞系HL-60中筛选出对钙离子载体（A23187）具有抗性的细胞（AR-7）。连续暴露3天后，与野生型细胞相比，AR-7对A23187的抗性约为8.5倍。AR-7对离子霉素（4.6倍）和毒胡萝卜素（340倍）具有交叉抗性，这两种物质也可增加细胞内钙离子浓度。孵育4小时后，观察到这些试剂诱导的细胞凋亡抗性程度相似，通过特征性形态和核小体间DNA片段化来定义。然而，在两种细胞类型中，用不同浓度的A23187刺激后细胞内钙离子浓度的升高以及对包括依托泊苷、1-β-D-阿拉伯糖基胞嘧啶和羟基脲在内的抗癌药物的敏感性相当。该细胞系被认为有助于探索钙离子载体诱导的细胞死亡机制，尤其是细胞凋亡机制。
