Saliev Timur, Feril Loreto B, Begimbetova Dinara, Baiskhanova Dinara, Klodzinskyi Anton, Bobrova Xeniya, Aipov Rassulbek, Baltabayeva Tolkyn, Tachibana Katsuro
National Laboratory Astana, Nazarbayev University, Astana, Kazakhstan.
Department of Anatomy, Fukuoka University School of Medicine, Fukuoka, Japan.
J Therm Biol. 2017 Jul;67:9-14. doi: 10.1016/j.jtherbio.2017.04.009. Epub 2017 Apr 28.
At present, the current therapeutic strategy for apoptosis induction mainly relies on the administration of pharmacological apoptotic modulators. Apart from that, apoptosis can be induced by various external stimuli such as hyperthermia, ionizing radiation, and electric fields. Despite advantages, both physical and pharmacological approaches bear some limitations as well. The rationale of this study was to overcome the limitations by combining hyperthermia and apoptotic modulator 'bortezomib' (Velcade). Two types of human blood cancer cell lines were utilized: human leukemic monocyte lymphoma cell U937 line and peripheral blood mononuclear cells (PMBCs) derived from the patient diagnosed with acute myeloid leukemia. Prior to apoptosis experiments, cytotoxicity tests were performed at three types of temperature regimes (40°, 42° and 44°C). We observed a gradual inhibition of cell viability correlating with an increase of temperature and drug concentration in both cell lines. However, there was no significant difference between sham group and groups of leukemic PMBCs treated by high temperature (44°C) and bortezomib. In U937 cells, combined treatment by heat shock and bortezomib led to an increase the number of cells underwent the late apoptosis stage. At the same time, similar treatment of PMBCs resulted in the stimulation of early apoptosis. Our data suggest that combination of bortezomib and hyperthermia enhances apoptosis induction in human cancer white blood cells, indicating a therapeutic potential for blood cancer therapy.
目前，诱导凋亡的当前治疗策略主要依赖于给予药理学凋亡调节剂。除此之外，凋亡可由多种外部刺激诱导，如热疗、电离辐射和电场。尽管有优点，但物理和药理学方法也都有一些局限性。本研究的基本原理是通过将热疗与凋亡调节剂“硼替佐米”（万珂）联合使用来克服这些局限性。使用了两种人类血癌细胞系：人白血病单核细胞淋巴瘤细胞U937系和来自诊断为急性髓性白血病患者的外周血单个核细胞（PMBCs）。在进行凋亡实验之前，在三种温度条件（40℃、42℃和44℃）下进行了细胞毒性试验。我们观察到两种细胞系中细胞活力逐渐受到抑制，且与温度和药物浓度的增加相关。然而，假手术组与经高温（44℃）和硼替佐米处理的白血病PMBCs组之间没有显著差异。在U937细胞中，热休克与硼替佐米联合处理导致晚期凋亡阶段的细胞数量增加。同时，对PMBCs进行类似处理导致早期凋亡受到刺激。我们的数据表明，硼替佐米与热疗联合可增强人癌白细胞中的凋亡诱导，这表明对血癌治疗具有治疗潜力。
