Jordan Andreas, Scholz Regina
Center of Biomedical Nanotechnology, Department of Radiology, Charité-University Medicine Berlin, Campus Virchow-Klinikum, Berlin, Germany.
Exp Oncol. 2005 Mar;27(1):18-23.
To generate heat resistant variants selected from established human gastric carcinoma cell lines exhibiting different types of multidrug resistance (MDR) phenotype, i.e. EPG85-257P, the drug sensitive parental cell-line, EPG85-257RDB, a classical MDR subline and EPG85-257RNOV, which is an atypical multidrug resistant subline.
Thermoresistance was induced by stepwise increase of the growth temperature from 37.0 to 39.4 degrees C. Thermoresistance was determined by change of population doubling time (PDT) and clonogenic survival after acute hyperthermia at 42, 43, 44 and 45 degrees C.
Most of the cells exhibited necrosis at elevated culture temperature. The PDT of the surviving thermoresistant variants were increased two-fold (EPG85-257P-TR) and 1.2-fold (EPG85-257RNOV-TR), respectively. No PDT change was observed with the lowest thermoresistant subline EPG85-257RDB-TR. Dose response curves after acute hyperthermia indicated a stable increase of thermotolerance of the parental cell line and the atypical MDR subline (50-90-fold at 45 degrees C), but not of the classical MDR subline, which was only increased at 43 degrees C (3-4-fold). Acquired thermoresistance did not change after freezing/thawing procedures.
All cell lines achieved chronically induced thermoresistance. Thermotolerance after acute hyperthermia was present in the drug sensitive parental cell line and the atypical MDR subline, but not in cells exhibiting a classical MDR phenotype.
从已建立的表现出不同类型多药耐药（MDR）表型的人胃癌细胞系中筛选出耐热变体，即药物敏感的亲本细胞系EPG85 - 257P、经典MDR亚系EPG85 - 257RDB和非典型多药耐药亚系EPG85 - 257RNOV。
通过将生长温度从37.0℃逐步升高至39.4℃诱导耐热性。通过群体倍增时间（PDT）的变化以及在42、43、44和45℃急性热疗后的克隆形成存活率来确定耐热性。
大多数细胞在升高的培养温度下表现出坏死。存活的耐热变体的PDT分别增加了两倍（EPG85 - 257P - TR）和1.2倍（EPG85 - 257RNOV - TR）。最低耐热亚系EPG85 - 257RDB - TR未观察到PDT变化。急性热疗后的剂量反应曲线表明，亲本细胞系和非典型MDR亚系的耐热性稳定增加（45℃时为50 - 90倍），但经典MDR亚系仅在43℃时增加（3 - 4倍）。冷冻/解冻程序后获得的耐热性没有变化。
所有细胞系均实现了长期诱导的耐热性。急性热疗后的耐热性存在于药物敏感的亲本细胞系和非典型MDR亚系中，但不存在于表现出经典MDR表型的细胞中。
