ABSTRACT
Myofibrillogenesis regulator-1 (MR-1) is a novel protein involved in cellular proliferation, migration, inflammatory reaction and signal transduction. However, little information is available on the relationship between MR-1 expression and the progression of atherosclerosis. Here we report atheroprotective effects of silencing MR-1 in a model of Ang II-accelerated atherosclerosis, characterized by suppression focal adhesion kinase (FAK) and nuclear factor kappaB (NF-κB) signaling pathway, and atherosclerotic lesion macrophage content. In this model, administration of the siRNA-MR-1 substantially attenuated Ang II-accelerated atherosclerosis with stabilization of atherosclerotic plaques and inhibited FAK, Akt, mammalian target of rapamycin (mTOR) and NF-kB activation, which was associated with suppression of inflammatory factor and atherogenic gene expression in the artery. In vitro studies demonstrated similar changes in Ang II-treated vascular smooth muscle cells (VSMCs) and macrophages: siRNA-MR-1 inhibited the expression levels of proinflammatory factor. These studies uncover crucial proinflammatory mechanisms of Ang II and highlight actions of silencing MR-1 to inhibit Ang II signaling, which is atheroprotective.
Subject(s)
Animals , Mice , Angiotensin II , Angiotensins , Arteries , Atherosclerosis , Cell Proliferation , Focal Adhesion Protein-Tyrosine Kinases , Gene Expression , In Vitro Techniques , Macrophages , Muscle Development , Muscle, Smooth, Vascular , NF-kappa B , Plaque, Atherosclerotic , RNA, Small Interfering , Signal Transduction , SirolimusABSTRACT
Objective Diallyl disulfide ( DADS) has achieved remarkable effects in treatment and research of diverserfied cancers.The article was to explore the effects and the mechanism of DADS on the xenograft growth of human small cell lung cancer ( SCLC) cells in nude mice . Methods A total of 25 nude mice were selected to establish xenograft model of NCI-H446 human SCLC cells.The nude mice bearing with SCLC H446 were divided into 5 groups by random selection:positive control group(DDP 66 mg/kg), negative control group(physiological saline), 20 mg/kg DADS group, 60 mg/kg DADS group and 180 mg/kg DADS group, which is 40.6%, 53.1%and 66.4%, respectively.The growth of xenograft tumor in mice was observed after being treated with differ-ent concentrations of DADS .The morphological changes of the tumors were examined under light microscopy .Phase distribution and apoptosis of xenograft cells were analyzed by flow cytometry ( FCM) . Results The growth of xenograft tumor were inhibited signifi-cantly by DADS, resulting in decreased cell density and cellular atypia .Moreover, xenograft cell cycle was blocked in G 2/M and cell apoptosis rate was enhanced . Conclusion DADS can significantly inhibit the growth of NCI-H446 cells and lead to apoptosis .
ABSTRACT
Aim To investigate the arrest effect of diallyl disulfide(DADS) in the cell cycle of human nasopharyngeal carcinoma SW480 cell line and its molecular mechanism.Mothdes The growth inhibition effect of DADS of different concentrations on SW480 cell line was measured by MTT assay and cell counting.Phase distribution of cell cycle was analyzed by flow cytometry.Expression of Ubiquitin and FKBP was determined by Western blot.Results The MTT assay showed that DADS inhibited growth of SW480 cells significantly in a dose-dependent manner.Adding 25,35,50 and 70 mg?L-1 DADS for 48 hours,SW480 cell growth was suppressed by 18.67%,33.02%,49.12% and 66.86%,respectively.There were significant differences between the treated and controlled cases(P