RESUMEN

Although cytotoxic chemotherapy is widely used against epithelial ovarian cancer (EOC), adverse side effects and emergence of resistance can limit its utility. Therefore, new drugs with systemic delivery platforms are urgently needed for this disease. In this study, we developed linalool-incorporated nanoparticles (LIN-NP) as a novel anticancer agent. We prepared LIN-NPs by the self-assembly water-in-oil-in-water (w/o/w) emulsion method. LIN-NP-mediated cytotoxicity and apoptosis was assessed in EOC cells, and the role of reactive oxygen species (ROS) generation as the mechanism of action was evaluated. In addition, therapeutic efficacy of LIN-NP was assessed in cell lines and patient-derived xenograft (PDX) models for EOC. LIN-NPs had significant cytotoxicity and apoptotic activity against EOC cells, including A2780, HeyA8, and SKOV3ip1. LIN-NP treatment increased apoptosis in EOC cells through ROS generation and a subsequent decrease in mitochondrial membrane potential and increase in caspase-3 levels. In addition, 100 mg/kg LIN-NPs significantly decreased tumor weight in the HeyA8 (P < 0.001) and SKOV3ip1 (P = 0.006) in vivo models. Although treatment with 50 mg/kg LIN-NP did not decrease tumor weight compared with the control group, combination treatment with paclitaxel significantly decreased tumor weight compared with paclitaxel alone in SKOV3ip1 xenografts (P = 0.004) and the patient-derived xenograft model (P = 0.020). We have developed LIN-NPs that induce ROS generation as a novel anticancer agent for EOC. These findings have broad applications for cancer therapy. Mol Cancer Ther; 15(4); 618-27. ©2016 AACR.

Asunto(s)

Antineoplásicos/administración & dosificación , Monoterpenos/administración & dosificación , Nanopartículas , Monoterpenos Acíclicos , Animales , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Carcinoma Epitelial de Ovario , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Quimioterapia Combinada , Femenino , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones , Monoterpenos/química , Nanopartículas/química , Neoplasias Glandulares y Epiteliales/tratamiento farmacológico , Neoplasias Glandulares y Epiteliales/metabolismo , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Paclitaxel/farmacología , Especies Reactivas de Oxígeno/metabolismo , Carga Tumoral/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto

RESUMEN

In this study, the disk type of a thermal barrier coating (TBC) system for a gas turbine blade was isothermally aged at 1100 degrees C for various times up to 400 hours. For each aging condition, the thickness of the thermally grown oxide (TGO) was measured by optical microscope and mechanical properties such as the elastic modulus and hardness were measured by micro-indentation and nano-indentation on the cross-section of a coating specimen. In the case of micro-indentation, the mechanical properties of a Ni-base superalloy substrate and MCrAlY bond coat material did not significantly change with an increase in exposure time. In the case of nano-indentation, the gamma-Ni phase and beta-NiAl phase in the bond coat and top coat material show no significant change in their properties. However, the elastic modulus and the hardness of TGO show a remarkable decrease from 100 h to 200 h then remain nearly constant after 200 h due to the internal delamination of TBC. It has been confirmed that the nano-indentation technique is a very effective way to evaluate the degradation of a thermal barrier coating system.