Efficacy of combined therapy with paclitaxel and low-level ultrasound in human chronic myelogenous leukemia cell line K562
Efficacy of combined therapy with paclitaxel and low-level ultrasound in human chronic myelogenous leukemia cell line K562
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DOI：
10.3109/1061186x.2013.830309
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发表时间：
2013-10
影响因子：
4.5
通讯作者：
Shuang Yang;Pan Wang;Xiaobing Wang;Kun Zhang;Xing Zhang;Quanhong Liu
中科院分区：
文献类型：
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作者：
Shuang Yang;Pan Wang;Xiaobing Wang;Kun Zhang;Xing Zhang;Quanhong Liu
摘要背景：声化学疗法是将超声应用于肿瘤化疗的一种新的治疗手段，已被研究证实是一种很有前途的治疗方法。目的：探讨低强度超声与紫杉醇（paclitaxel，PTX）联合应用对人慢性粒细胞白血病细胞株K562的作用及联合应用的疗效，并探讨其在声化疗中的作用机制。方法：采用MTT法和GuavaViacount法检测细胞活力。使用Annexin V-PE/7-氨基-放线菌素D染色分析细胞凋亡。通过FD 500摄取和乳酸脱氢酶（LDH）释放测定监测质膜通透性的变化。扫描电镜下观察超微结构变化。结果如下：当5 ng/ml PTX与负载功率（LP）= 2 W的超声联合作用时，可检测到预期的协同效应，细胞活力丧失（p < 0.05）和凋亡增强，质膜通透性显示出最好的反应，SEM下观察到相对严重的细胞损伤。结论：这两种治疗之间的相互作用取决于特定的参数设置，如PTX剂量和超声强度。在协同作用下，超声可显著增强PTX的细胞毒性、凋亡和细胞损伤诱导作用，其机制可能与超声增强细胞膜通透性和增加细胞内PTX水平有关。
Abstract Background: Sonochemotherapy, which applies ultrasound in cancer chemotherapy, has been proven to be a promising therapeutic modality by some previous researches. Purpose: To investigate the interaction between an antineoplastic agent – paclitaxel (PTX) and low-level ultrasound in human chronic myelogenous leukemia cell line K562, their combined efficacy, and the potential mechanisms in sonochemotherapy. Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) analysis and Guava Viacount assay were adopted to examine cell viability. Apoptosis was analyzed using Annexin V-PE/7-amino-actinomycin D staining. Changes in plasma membrane permeability were monitored by FD500-uptake and lactate dehydrogenase (LDH) release assays. Additionally, the ultrastructure changes were evaluated under scanning electron microscope (SEM). Results: When 5 ng/ml PTX was combined with sonication at Load Power (LP) = 2 W, the expected synergistic effects on cell viability loss (p < 0.05) and apoptosis enhancement could be significantly detected, the plasma membrane permeability showed the best response, and relatively serious cell damages were observed under SEM. Conclusion: The interaction between these two therapies depended on specific parameter settings, such as PTX dose and ultrasound intensity. Under synergistic conditions, ultrasound significantly potentiated the efficacies of PTX, including cytotoxicity, apoptosis and cell damage induction, which may be due to the enhanced membrane permeability and the increased intracellular PTX level.