Barros Andre, Austerlitz Carlos, Gkigkitzis Ioannis, Campos Diana, Andrade Jeyce, Peixoto Christina, Aguiar Jaciana, Nascimento Silene, Silva Teresinha G, Haranas Ioannis
Bioassays Laboratory for Pharmaceutical Research, Antibiotics Department, Biological Sciences Center, Federal University of Pernambuco, Recife, Brazil.
Department of Computer Science, Southern Illinois University, Carbondale, IL, 62901, USA.
Adv Exp Med Biol. 2017;987:119-138. doi: 10.1007/978-3-319-57379-3_12.
The aim of this study was to analyze feasibility (in vitro and in vivo) the use of hyperthermia produced by gold rods irradiated with ultrasound and their combination with chemotherapy with doxorubicin.
initially was determined the cell viability and Hsp70 levels after treatment by gold rods irradiated with ultrasound (GR+U) in cell culture. The pretreatment with GR+U combined with doxorubicin (DOX) was evaluated from IC, caspase-3 expression and mechanisms of cell death by electron microscopy. For evaluate the in vivo effects was used solid Ehrlich carcinoma (SEC) Tumor. The animals received three treatments with the combination of GR+U+DOX over 16 days.
The cell viability was completely inhibited after 40 min of treatment with GR+U and significant increases the expression of HSP70 was only observed after 10 min of treatment. GR+U+DOX presented significant reduction of IC representing 50.7%, 76.5% 45.2% and 46.6% for cell lines K562, NCI-H292, Hep-2 and MCF-7 respectively. GR+U+DOX presented significant reduction of IC representing 50.7%, 76.5% 45.2% and 46.6% for cell lines K562, NCI-H292, Hep-2 and MCF-7 respectively. The caspase-3 level and ultraestructural analysis showed that treatment with GR+U+DOX enhances induction of apoptosis. Pretreatment with GR+U combined with doxorubicin (1 mg) showed 87% inhibition against SEC. and no showed cardiotoxic effect.
The combined treatment of GR+U and DOX exhibit synergistic characteristics observed by increasing the efficiency of doxorubicin.
本研究旨在分析用超声照射金棒产生的热疗及其与阿霉素化疗联合使用的可行性(体外和体内)。
首先在细胞培养中测定经超声照射的金棒(GR+U)处理后的细胞活力和热休克蛋白70(Hsp70)水平。通过电子显微镜从半数抑制浓度(IC)、半胱天冬酶-3表达和细胞死亡机制评估GR+U联合阿霉素(DOX)的预处理情况。为评估体内效果,使用实体艾氏癌(SEC)肿瘤。动物在16天内接受三次GR+U+DOX联合治疗。
用GR+U处理40分钟后细胞活力被完全抑制,仅在处理10分钟后观察到HSP70表达显著增加。GR+U+DOX使K562、NCI-H292、Hep-2和MCF-7细胞系的IC分别显著降低50.7%、76.5%、45.2%和46.6%。GR+U+DOX使K562、NCI-H292、Hep-2和MCF-7细胞系的IC分别显著降低50.7%、76.5%、45.2%和46.6%。半胱天冬酶-3水平和超微结构分析表明,GR+U+DOX处理增强了凋亡诱导。GR+U联合阿霉素(1毫克)预处理对SEC显示出87%的抑制作用,且未显示出心脏毒性作用。
GR+U和DOX的联合治疗通过提高阿霉素的效率表现出协同特性。