Synergistic Effect of NF-κB Signaling Pathway Inhibitor and Oncolytic Measles Virus Vaccine Strain against Lung Cancer and Underlying Mechanisms / 中国肺癌杂志

BACKGROUND@#Lung cancer is one of the leading causes of cancer-related morbidity and mortality. Oncolytic virotherapy is an emerging therapeutic modality that utilizes replication-competent viruses to destroy cancers. As a powerful tool to kill tumor cells with excellent safety profile, attenuated measles virus of the Edmonston strain (MV-Edm) has been widely applied in the development of tumor therapy and preclinical trials. The aim of this study was to investigate the synergistic effect of nuclear factor kappa B (NF-κB) signaling pathway inhibitor and oncolytic measles virus vaccine against lung cancer and the involved mechanisms.@*METHODS@#Using Western blot to detect MV-Edm infection of A549 and H1299 were infected by MV-Edm alone or used the NF-κB pathway inhibitor PS1145/cell autophagy related siRNA, expression level of p-IκBα, IκBα, PARP and BAX were determined by western blot. Using flow cytometry to analysis the rate of apoptosis, and using MTT [3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide] method to detect the cell survival rate.@*RESULTS@#Inhibition of cell autophagy could obviously inhibit the MV-Edm infection induced the NF-κB pathway activation in A549 and H1299. In MV-Edm infected A549 and H1299, p-IκBα level increased and IκBα level decreased over infection time, compared with control group. Inhibition of the NF-κB pathway by PS1145 could promote the apoptosis of MV-Edm infected A549 and H1299 and amplify the tumor killing effect.@*CONCLUSIONS@#The combination of NF-κB signaling pathway inhibitor pS1145 and oncolytic measles virus vaccine strains can promote the apoptosis of human lung cancer cells A549 and H1299 and enhance their oncolytic effect.

Islet Insulin Secretion, β-Cell Mass, and Energy Balance in a Polygenic Mouse Model of Type 2 Diabetes With Obesity

Abstract Type 2 diabetes (T2D) and obesity are polygenic metabolic diseases, highly prevalent in humans. The TALLYHO/Jng (TH) mouse is a polygenic model of T2D and obesity that encompasses many aspects of the human conditions. In this study, we investigated the key metabolic components including β-cell physiology and energy balance involved in the development of diabetes and obesity in TH mice. Glucose-stimulated insulin secretion from freshly isolated islets was significantly enhanced in TH mice compared with normal C57BL/6 (B6) mice, similar to the compensated stage in human T2D associated with obesity. This increased glucose responsiveness was accompanied by an increase in total β-cell mass in TH mice. Energy expenditure and locomotor activity were significantly reduced in TH mice compared with B6 mice. Food intake was comparable between the two strains but water intake was more in TH mice. Together, obesity in TH mice does not appear to be due to hyperphagia, and TH mice may be a genetic model for T2D with obesity, allowing study of the important signaling or metabolic pathways leading to compensatory increases in insulin secretion and β-cell mass in insulin resistance.