Shuang Yang1, Pan Wang, Xiaobing Wang, Kun Zhang, Xing Zhang, Quanhong Liu. 1. Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, Ministry of Education, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University , Xi'an, Shaanxi , China.
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.
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.