Gabai V L, Zamulaeva I V, Mosin A F, Makarova Y M, Mosina V A, Budagova K R, Malutina Y V, Kabakov A E
Medical Radiology Research Center, Russian Academy of Medical Sciences, Obninsk, Russian Federation.
FEBS Lett. 1995 Nov 13;375(1-2):21-6. doi: 10.1016/0014-5793(95)01152-5.
Previously we have found that stationary Ehrlich ascites carcinoma (EAC) cells in vivo accumulated heat shock proteins (HSPs) and became resistant to necrotic death induced by prolonged energy deprivation of hyperthermia. Here we report that apoptotic death induced by nutrient starvation, transient ATP depletion, heat shock and a microtubule-disrupting drug, vinblastine, was also suppressed in stationary EAC cells comparing with exponential cells. When exponential (sensitive) cells were subjected to short-term heating with recovery to accumulate inducible form of HSP70, they also became resistant to all of the employed apoptosis-inducing exposures, and an inhibitor of cytosolic protein synthesis, cycloheximide, prevented acquisition of the resistance. It is suggested that in vivo accumulation of HSPs in stationary tumor cells can be endogenous protective device against apoptotic death induced by starvation or some anticancer treatments.
此前我们发现,体内静止的艾氏腹水癌细胞(EAC)会积累热休克蛋白(HSPs),并对因长时间高温导致能量剥夺所诱导的坏死性死亡产生抗性。在此我们报告,与指数生长期细胞相比,营养饥饿、短暂ATP耗竭、热休克以及一种破坏微管的药物长春碱所诱导的凋亡性死亡,在静止的EAC细胞中也受到抑制。当指数生长期(敏感)细胞进行短期加热并恢复以积累诱导型HSP70时,它们同样对所有采用的凋亡诱导刺激产生抗性,并且一种胞质蛋白合成抑制剂环己酰亚胺可阻止抗性的获得。这表明静止肿瘤细胞中HSPs的体内积累可能是一种针对饥饿或某些抗癌治疗所诱导的凋亡性死亡的内源性保护机制。