Thermal cycling as a novel thermal therapy to synergistically enhance the anticancer effect of propolis on PANC-1 cells
Thermal cycling as a novel thermal therapy to synergistically enhance the anticancer effect of propolis on PANC-1 cells
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DOI：
10.3892/ijo.2019.4844
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发表时间：
2019-09-01
影响因子：
5.2
通讯作者：
Chao, Chih-Yu
中科院分区：
文献类型：
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作者：
Chen, Wei-Ting;Sun, Yi-Kun;Chao, Chih-Yu
热疗（HT）在癌症治疗中显示出潜力。特别是，它似乎使癌细胞对化疗敏感。然而，与HT相关的一个主要问题是，应用于肿瘤细胞的热剂量也可能损害正常组织细胞。此外，HT中使用的药物是常规化疗药物，可能会引起严重的副作用。本研究展示了一种新的HT治疗方法，称为热循环（TC）-HT。通过这种策略，通过将TC-HT与天然化合物组合，创造了具有最大协同效应的治疗窗口，并具有最小的不必要的细胞损伤。选择天然化合物雷公藤多甙，研究了TC-HT和雷公藤多甙对胰腺癌细胞的协同抗肿瘤作用。本研究结果首次证实了TC-HT可通过抑制PANC-1细胞的凋亡和细胞周期阻滞来增强顺铂对PANC-1细胞的抗癌作用。联合治疗大大抑制了线粒体膜电位，这是线粒体受损和功能障碍的重要指标。此外，细胞周期调节蛋白细胞分裂周期蛋白2在联合处理后下调，这阻止了细胞向有丝分裂的进展。本研究提供了第一份报告，据我们所知，TC-HT与天然化合物相结合，用于胰腺癌治疗。预计这种方法可能是更复杂的癌症治疗的起点，从而可能改善许多癌症患者的生活质量。
Hyperthermia (HT) has shown potential in cancer therapy. In particular, it appears to sensitize cancer cells to chemotherapy. However, a major concern associated with HT is that the thermal dosage applied to the tumor cells may also harm the normal tissue cells. Besides, the drugs used in HT are conventional chemotherapy drugs, which may cause serious side effects. The present study demonstrated a novel methodology in HT therapy called thermal cycle (TC)-HT. With this strategy, a therapeutic window with a maximum synergistic effect was created by combining TC-HT with natural compounds, with minimal unwanted cell damage. The natural compound propolis was selected, and the synergistic anticancer effect of TC-HT and propolis was investigated in pancreatic cancer cells. The present results demonstrated for the first time that TC-HT could enhance the anticancer effect of propolis on PANC-1 cancer cells through the mitochondria-dependent apoptosis pathway and cell cycle arrest. Combined treatment greatly suppressed mitochondrial membrane potential, which is an important indicator of damaged and dysfunctional mitochondria. Furthermore, the cell cycle-regulating protein cell division cycle protein 2 was downregulated upon combined treatment, which prevented cellular progression into mitosis. The present study offers the first report, to the best of our knowledge, on the combination of TC-HT with a natural compound for pancreatic cancer treatment. It is anticipated that this methodology may be a starting point for more sophisticated cancer treatments and may thereby improve the quality of life of many patients with cancer.