bm-567 and furegrelate

bm-567 has been researched along with furegrelate* in 2 studies

*furegrelate: structure given in UD 35:175:d [MeSH]

*furegrelate: structure given in UD 35:175:d [MeSH]

Other Studies

2 other study(ies) available for bm-567 and furegrelate

ArticleYear
Thromboxane A2 exerts promoting effects on cell proliferation through mediating cyclooxygenase-2 signal in lung adenocarcinoma cells.
    Journal of cancer research and clinical oncology, 2014, Volume: 140, Issue:3

    Lung cancer concerns a worldwide health problem and the efficacy of available treatments is unsatisfactory. Recently, thromboxane A2 (TXA2) synthase (TXAS) and receptor (TXA2R) have been documented to play a role in lung cancer development. Therefore, dual TXA2R modulator (i.e., the dual blocker of TXAS and TXA2R) may be more efficacious to kill lung tumor cells than single TXAS inhibitor or TXA2R antagonism. The close relationship between cyclooxygenase (COX)-2 and TXAS also raises whether or how TXA2 contributes to the oncogenic activity of COX-2. This study is therefore conducted to answer these questions.. Various inhibitors and siRNA were used to evaluate the roles of TXA2 and COX-2 in the proliferation and apoptosis of lung adenocarcinoma cells. Cell proliferation was detected using both MTS ELISA and BrdU labeling ELISA. Cell cycle distribution and apoptosis were examined by flow cytometric analysis. TXB2 level, reflecting the biosynthesis of TXA2, was detected by peroxidase-labeled TXB2 conjugates using an enzyme immunoassay kit. Western blotting was performed to evaluate many biomarkers for cell cycles, apoptosis and proliferation. The levels of COXs were screened by reverse transcriptase and real-time quantitative PCR.. We found either single TXAS inhibitor/TXA2R antagonist or the dual TXA2 modulators offered a similar inhibition on cell proliferation. Moreover, inhibition of TXA2 arrested cells at the G2/M phase and induced apoptosis. It is further demonstrated that TXA2 was able to function as a critical mediator for tumor-promoting effects of COX-2 in lung adenocarcinoma cells.. The present study has for the first shown that dual TXA2 modulators and the single blocker of TXAS or TXA2R offer a similar inhibitory role in lung adenocarcinoma cell proliferation and that the tumor-promoting effects of COX-2 can largely be relayed by TXA2. Thus, TXA2 should be regarded as a critical molecule in COX-2-mediated tumor growth and a valuable target against lung cancer.

    Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Adenocarcinoma; Adenocarcinoma of Lung; Antineoplastic Agents; Apoptosis; Benzofurans; Blotting, Western; Bridged Bicyclo Compounds, Heterocyclic; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cyclooxygenase 2; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Enzyme-Linked Immunosorbent Assay; Fatty Acids, Unsaturated; Flow Cytometry; Humans; Hydrazines; Immunoenzyme Techniques; Lung Neoplasms; Nitrobenzenes; Real-Time Polymerase Chain Reaction; Receptors, Thromboxane; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Sulfonamides; Sulfonylurea Compounds; Thromboxane A2; Thromboxane-A Synthase

2014
Kupffer cell depletion attenuates leptin-mediated methoxamine-stimulated portal perfusion pressure and thromboxane A2 release in a rodent model of NASH-cirrhosis.
    Clinical science (London, England : 1979), 2012, Volume: 123, Issue:12

    Cirrhotic portal hypertension is characterized by increased hepatic oxidative stress, AA (arachidonic acid)-derived TXA(2) (thromboxane A(2)) release and exaggerated hepatic response to the α-adrenergic agonist MTX (methoxamine). Besides promoting hepatic fibrosis, the role of hyperleptinaemia in the modulation of vascular response in NASH (non-alcoholic steatohepatitis) rat livers remains unknown. The aim of the present study was to explore the possible links between hyperleptinaemia and the disarrangement in the hepatic microcirculation. NASH-cirrhosis with hyperleptinaemia was induced in lean rats by feeding with an HF/MCD (high-fat/methionine-choline-deficient) diet. Portal haemodynamics, various substances, protein and mRNA expression and PUFA (polyunsaturated fatty acid) composition were measured. Finally, the effects of leptin pre-infusion on TXA(2) release and concentration-PPP (portal perfusion pressure) curves in response to MTX were evaluated by simultaneously pre-treatment with the Kupffer cell inactivators GdCl(3) (gadolinium chloride) or EC (encapsulated clodronate), the TXS (TXA(2) synthase) inhibitor furegrelate, the TP receptor (TXA(2) receptor) antagonist SQ29548 and the dual TXS/TP receptor antagonist BM567. In HF/MCD+leptin-lean rats, cirrhosis-induced PPP and MTX hyper-responsiveness were associated with increased hepatic TXA(2) production, TBARS (thiobarbituric acid-reacting substances) levels and the AA (arachidonic acid)/n-3 PUFA ratio, and up-regulation of hepatic leptin, FAS (fatty acid synthase), NADPH oxidase subunits, TXS, TP receptor, TGFβ(1) (transforming growth factor β(1)) proteins and mRNAs. Pre-infusion of leptin significantly enhanced MTX-stimulated PPP elevation and TXA(2) release, which were attenuated by GdCl(3) and EC pre-treatment. Concomitantly pre-incubation with BM567, but not furegrelate or SQ29548, significantly abolished the leptin-enhanced MTX-stimulated increase in PPP in NASH-cirrhotic rats. Hyperleptinaemia plays an important role in hyper-responsiveness to MTX in NASH-cirrhotic rat livers with portal hypertension. The leptin-enhanced MTX-stimulated increase in PPP is mediated by increased oxidative stress and Kupffer-cell-activated AA-derived TXA(2) release in NASH-cirrhotic rats.

    Topics: Analysis of Variance; Animals; Arachidonic Acid; Benzofurans; Choline; Clodronic Acid; Diet, High-Fat; DNA Primers; Fatty Acids, Unsaturated; Fatty Liver; Gadolinium; Hemodynamics; Hypertension, Portal; Insulin Resistance; Kupffer Cells; Leptin; Methionine; Methoxamine; Microcirculation; Non-alcoholic Fatty Liver Disease; Oxidative Stress; Rats; Receptors, Thromboxane A2, Prostaglandin H2; RNA, Messenger; Sulfonylurea Compounds; Thiobarbituric Acid Reactive Substances; Thromboxane A2

2012
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