Studies on the non-invasive anticancer remedy of the triple combination of epigallocatechin gallate, pulsed electric field, and ultrasound
Studies on the non-invasive anticancer remedy of the triple combination of epigallocatechin gallate, pulsed electric field, and ultrasound
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DOI：
10.1371/journal.pone.0201920
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发表时间：
2018-08-06
期刊：
影响因子：
3.7
通讯作者：
Chao, Chih-Yu
中科院分区：
文献类型：
--
作者：
Hsieh, Chih-Hsiung;Lu, Chueh-Hsuan;Chao, Chih-Yu
癌症是世界上最麻烦的疾病之一，也是导致死亡的主要原因之一。最近，新的治疗方法不断发展，以改善传统治疗方法的缺点，如巨大的费用，不良的副作用，肿瘤复发。在这里，我们提供了第一个非侵入性治疗，结合了表没食子儿茶素没食子酸酯（EGCG），绿茶中最丰富的儿茶素，低强度脉冲电场（PEF）和低能超声（US）。研究发现，在此联合治疗72小时后，人胰腺癌PANC-1的细胞活力下降约为对照组的20%。此外，三联治疗显著降低了HepG2细胞对egcg诱导的细胞毒性的高耐受性，同样表现出令人注目的增殖抑制作用。我们还发现三重联合处理增加了细胞内活性氧（ROS）和酸性囊泡，并且egcg诱导的Akt磷酸化抑制显著增强。在本研究中，细胞凋亡抑制剂Z-VAD-FMK和自噬抑制剂3-MA分别被证明可以减弱三联治疗的抗癌作用。这表明三重治疗诱导的自噬从细胞保护性转变为细胞毒性，从而与细胞凋亡共同导致细胞死亡。由于EGCG很容易从绿茶中获得，并且长期治疗温和，并且非侵入性物理刺激可以修改为专注于特定部位，这种三联疗法可能是一种很有前途的抗癌治疗策略。
Cancer is one of the most troublesome diseases and a leading cause of death worldwide. Recently, novel treatments have been continuously developed to improve the disadvantages of conventional therapies, such as prodigious expenses, unwanted side effects, and tumor recurrence. Here, we provide the first non-invasive treatment that has combined epigallocatechin gallate (EGCG), the most abundant catechin in green tea, with a low strength pulsed electric field (PEF) and a low energy ultrasound (US). It has been observed that the cell viability of human pancreatic cancer PANC-1 was decreased approximately to 20% of the control after this combination treatment for 72 h. Besides, the combined triple treatment significantly reduced the high tolerance of HepG2 cells to the EGCG-induced cytotoxicity and similarly exhibited compelling proliferation-inhibitory effects. We also found the combined triple treatment increased the intracellular reactive oxygen species (ROS) and acidic vesicles, and the EGCG-induced inhibition of Akt phosphorylation was dramatically intensified. In this study, the apoptosis inhibitor Z-VAD-FMK and the autophagy inhibitor 3-MA were, respectively, shown to attenuate the anticancer effects of the triple treatment. This indicates that the triple treatment-induced autophagy was switched from cytoprotective to cytotoxic, and hence, cooperatively caused cell death with the apoptosis. Since the EGCG is easily accessible from the green tea and mild for a long-term treatment, and the non-invasive physical stimulations could be modified to focus on a specific location, this combined triple treatment may serve as a promising strategy for anticancer therapy.