Morrissey Joseph J, Higashikubo Ryuji, Goswami Prabhat C, Dixon Philip
College of Pharmacy, Nova Southeastern University, Ft. Lauderdale, FL 33328, USA.
J Drug Target. 2009 Nov;17(9):719-23. doi: 10.3109/10611860903074968.
The effect of mild hyperthermia on growth kinetics of two human glioma and one mouse fibroblast cell line was evaluated over a 12 h (short-term) or 7 day (long-term) period. All cell lines showed growth enhancement at 38 degrees C, although the effect in C3H 10T (1/2) mouse fibroblasts was more pronounced and had a more rapid onset than in U87MG or LN71 glioma cells. At 39 degrees C, growth of C3H 10T (1/2) cells was slightly reduced and glioma cell lines similar to that of their respective 37 degrees C controls. At 40 degrees C, C3H 10T (1/2) cells showed a more rapid and dramatic growth reduction than glioma cell lines and accumulated in both G(0)/G(1) and G(2) checkpoint compartments. In contrast, U87MG cells accumulated only in G(2) and LN71 showed no checkpoint accumulation. The findings indicate that cell lines are differentially responsive to small temperature elevations. If similar differences exist between normal and diseased human tissues, local application of mild hyperthermia might offer a noninvasive and cost-effective method to achieve local enhancement of drugs that target proliferating tissue.
在12小时(短期)或7天(长期)内评估了轻度热疗对两种人类胶质瘤细胞系和一种小鼠成纤维细胞系生长动力学的影响。所有细胞系在38℃时均显示出生长增强,尽管C3H 10T(1/2)小鼠成纤维细胞中的这种效应比U87MG或LN71胶质瘤细胞更明显且起效更快。在39℃时,C3H 10T(1/2)细胞的生长略有减少,而胶质瘤细胞系的生长与各自37℃对照相似。在40℃时,C3H 10T(1/2)细胞比胶质瘤细胞系表现出更快且更显著的生长减少,并在G(0)/G(1)和G(2)检查点区室中积累。相比之下,U87MG细胞仅在G(2)中积累,而LN71则未显示检查点积累。这些发现表明细胞系对小幅度温度升高的反应存在差异。如果正常和患病的人体组织之间存在类似差异,那么局部应用轻度热疗可能提供一种非侵入性且经济有效的方法,以实现对靶向增殖组织的药物的局部增强作用。