Kampinga Harm H
Department of Cell Biology, Section of Radiation & Stress Cell Biology, University of Groningen, UMCG, Groningen, The Netherlands.
Int J Hyperthermia. 2006 May;22(3):191-6. doi: 10.1080/02656730500532028.
Hyperthermia results in protein unfolding that, if not properly chaperoned by Heat Shock Proteins (HSP), can lead to irreversible and toxic protein aggregates. Elevating HSP prior to heating makes cells thermotolerant. Hyperthermia also can enhance the sensitivity of cells to radiation and drugs. This sensitization to drugs or radiation is not directly related to altered HSP expression. However, altering HSP expression before heat and radiation or drug treatment will affect the extent of thermal sensitization because the HSP will attenuate the heat-induced protein damage that is responsible for radiation- or drug-sensitization. For thermal radiosensitization, nuclear protein damage is considered to be responsible for hyperthermic effects on DNA repair, in particular base excision repair. Hyperthermic drug sensitization can be seen for a number of anti-cancer drugs, especially of alkylating agents. Synergy between heat and drugs may arise from multiple events such as heat damage to ABC transporters (drug accumulation), intra-cellular drug detoxification pathways and repair of drug-induced DNA adducts. This may be why cells with acquired drug resistance (often multi-factorial) can be made responsive to drugs again by combining the drug treatment with heat.
热疗会导致蛋白质解折叠，如果没有热休克蛋白（HSP）进行适当的伴侣作用，可能会导致不可逆的毒性蛋白质聚集体。在加热前提高HSP水平可使细胞产生热耐受性。热疗还可增强细胞对辐射和药物的敏感性。这种对药物或辐射的敏感性增加与HSP表达的改变没有直接关系。然而，在热疗、辐射或药物治疗前改变HSP的表达会影响热敏化的程度，因为HSP会减轻导致辐射或药物敏化的热诱导蛋白质损伤。对于热辐射增敏作用，核蛋白损伤被认为是热疗对DNA修复，特别是碱基切除修复产生影响的原因。许多抗癌药物，尤其是烷基化剂，都可出现热疗药物增敏作用。热疗与药物之间的协同作用可能源于多种事件，如热损伤ABC转运蛋白（药物蓄积）、细胞内药物解毒途径以及药物诱导的DNA加合物的修复。这可能就是为什么具有获得性耐药性（通常是多因素的）的细胞通过将药物治疗与热疗相结合可以再次对药物产生反应的原因。
