Effects of Compound Danshen tablets on spatial cognition and expression of brain β-amyloid precursor protein in a rat model of alzheimer's disease

AbstractObjectiveTo observe the effects of Compound Danshen Tablets (CDST) on spatial cognition and expression of brain b-amyloid precursor protein (β-APP) in a rat model of Alzheimer's disease.MethodsThe rat model of Alzheimer's disease (AD) was established using D-galactose to cause subacute aging combined with Meynert nucleus damage. Rat behavior was monitored using the Morris water maze, and the expression of β-APP in rat brain tissue was detected via immunohistochemistry.ResultsCDST significantly improved spatial cognition and decreased β-APP expression in the cortex and hippocampus (P<0.05, P<0.01).ConclusionsCDST can significantly improve spatial cognition in a rat model of AD. This observation is possibly related to a reduction in β-APP expression in the rat brain

Ku80 cooperates with CBP to promote COX-2 expression and tumor growth.

Cyclooxygenase-2 (COX-2) plays an important role in lung cancer development and progression. Using streptavidin-agarose pulldown and proteomics assay, we identified and validated Ku80, a dimer of Ku participating in the repair of broken DNA double strands, as a new binding protein of the COX-2 gene promoter. Overexpression of Ku80 up-regulated COX-2 promoter activation and COX-2 expression in lung cancer cells. Silencing of Ku80 by siRNA down-regulated COX-2 expression and inhibited tumor cell growth in vitro and in a xenograft mouse model. Ku80 knockdown suppressed phosphorylation of ERK, resulting in an inactivation of the MAPK pathway. Moreover, CBP, a transcription co-activator, interacted with and acetylated Ku80 to co-regulate the activation of COX-2 promoter. Overexpression of CBP increased Ku80 acetylation, thereby promoting COX-2 expression and cell growth. Suppression of CBP by a CBP-specific inhibitor or siRNA inhibited COX-2 expression as well as tumor cell growth. Tissue microarray immunohistochemical analysis of lung adenocarcinomas revealed a strong positive correlation between levels of Ku80 and COX-2 and clinicopathologic variables. Overexpression of Ku80 was associated with poor prognosis in patients with lung cancers. We conclude that Ku80 promotes COX-2 expression and tumor growth and is a potential therapeutic target in lung cancer