I Did Not Realize That!: Top 17 c-Met InhibitorDecitabine Of The Era

h of human gastric cancer cells remains unexplored. Survivin, the 16.5 kDa protein, first described in 1997, is a member of the inhibitor of c-Met Inhibitor apoptosis protein IAP family members 4 . Survivin is overexpressed in fetal tissue, rapidly dividing cells, like stem and progenitor cells, and inside a selection of human malignancies 4,5 . It suppresses apoptosis by inhibiting pro apoptotic caspases 3 and 7, and promotes cell cycle progression by acting as a microtubule stabilizer during mitosis 6 9 . A sustained overexpression of survivin is a characteristic feature of gastric cancer, where by inhibiting apoptosis and facilitating mitosis, it provides cancer cells, a survival and growth advantage 10 14 . Limited studies demonstrated that in gastric cancer expression of survivin plays an essential function in tumor progression and resistance of malignant cells to anti cancer drugs 10 14 .
Our previous studies demonstrated that survivin is expressed in normal human gastric mucosa and is temporarily overexpressed c-Met Inhibitor in the epithelial cells of gastric ulcer margin where it plays protective and ulcer Decitabine healing promoting roles 15,16 . Aurora family members of serine threonine kinases is extremely conserved Human musculoskeletal system in eukaryotes, is essential in some cells for a correct progression of mitosis, and is involved in several processes involved in cell division 17 23 . Aurora B is a chromosomal passenger protein important for chromosome alignment and cytokinesis 17 23 . It concentrates at centromeres and relocates to the central spindle in anaphase 17 23 .
Aurora B plays roles in spindle dynamics, chromosome condensation, and cytokinesis by interacting with other proteins like INCENP, survivin, and intermediate filaments Decitabine 17 23 . Overexpression of both Aurora A and Aurora B frequently occurs inside a selection of human cancers 22,23 . Surprisingly, the expression of Aurora B in human gastric cancer has not been explored just before. This study was aimed to figure out: 1 expression and cellular localization of survivin and Aurora B in human gastric cancer AGS cells and 2 to examine in gastric cancer AGS cells the effect of: a downregulation of survivin with distinct siRNA and b therapy with rebamipide on survivin and Aurora B expression and cell proliferation. Considering that ubiquitin proteasome pathway is a significant cellular approach of survivin degradation 24 , we examined whether rebamipide induced downregulation of survivin occurs via the ubiquitin proteasome mechanism.
This study demonstrates for the first time that Aurora B is strongly expressed in human gastric cancer AGS cells and binds in these cells to survivin in the mitotic spindle. It further shows c-Met Inhibitor that anti ulcer drug rebamipide arrests growth and proliferation of human gastric cancer cells by lowering survivin and Aurora B expression. Rebamipide induced downregulation of survivin is at the transcription Decitabine level and does not involve ubiquitin proteasome degradation pathway. Survivin mRNA and protein are strongly expressed in gastric cancer AGS cells as reflected by RT PCR Inhibitor 1A , Western blotting Inhibitor 1B , and immunostaining Figs. 1C and 2A . Immunostaining demonstrated expression of survivin in 52 of cancer cells, strong staining predominantly localized to the nuclei Figs.
1C and 2A . Aurora B is also strongly expressed in AGS cells, typically co expressed and co localized with survivin, especially in the mitotic c-Met Inhibitor spindle of cells undergoing divisions Figs. 2B and C . Treatment with distinct survivin siRNA significantly knock down survivin expression Figs. 3A and B and significantly reduced cell viability Inhibitor 3C . Treatment with rebamipide significantly reduced survivin mRNA and protein expression Figs. 4A, B and 5 and reduced Aurora B Inhibitor 5 and cell proliferation Inhibitor 6 . Pretreatment with all the proteasome inhibitor, MG 132, did not affect rebamipide induced downregulation of survivin in AGS cells data not shown , indicating that ubiquitin proteasome pathway is just not involved in the mechanism of rebamipide action on survivin in AGS cells.
This study demonstrated that survivin is strongly expressed in human gastric cancer AGS cells and that antiulcer drug, rebamipide, Decitabine strongly downregulates survivin expression. This downregulation is at the transcription level, given that rebamipide did significantly minimize survivin mRNA. Since the ubiquitin proteasome pathway regulates survivin degradation in some cells 24 which includes human hepatocellular carcinoma cell lines 27 , we examined whether proteasome inhibitor, MG 132, affects rebamipide induced survivin downregulation. The proteasome inhibitor, MG 132, did not affect rebamipide induced downregulation of survivin in AGS cells, which clearly indicates that proteasome degradation pathway is just not involved in survivin downregulation by rebamipide. Downregulation of survivin preceded a considerable inhibition of AGS cell proliferation reflected by reduced 3H thymidine uptake and a dramatic reduction in the number of mitotic figures. This finding underscores the important function of su