PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 29257256-9 2018 Taken together, the preclinical results of the present study indicate that simvastatin is efficient in preventing memory lapse and inhibiting apoptosis of hippocampal cells via the ERK/AKT signaling pathway, which may in the future improve cognitive decline and dementia in patients. Simvastatin 75-86 AKT serine/threonine kinase 1 Homo sapiens 185-188 31839714-0 2019 Statins induce cell apoptosis through a modulation of AKT/FOXO1 pathway in prostate cancer cells. Simvastatin 0-7 AKT serine/threonine kinase 1 Homo sapiens 54-57 31839714-10 2019 Conclusion: Statins decrease cell proliferation and induce cell apoptosis, probably mediated via a downregulation of AKT/FOXO1 phosphorylation in prostate cancer cells, which may have a potential benefit in prostate cancer prevention and therapy. Simvastatin 12-19 AKT serine/threonine kinase 1 Homo sapiens 117-120 29865262-8 2018 Akt or VDR knockdown by siRNA counteracted the suppressive effect of simvastatin on IL-8 expression, whereas VDR knockdown diminished the enhanced hBD-2 expression in Salmonella-infected SW480 cells. Simvastatin 69-80 AKT serine/threonine kinase 1 Homo sapiens 0-3 29435052-14 2018 Furthermore, treatment with simvastatin attenuated insulin-like growth factor 1-induced Akt activation; however, the combination of simvastatin and meclofenamic acid further inhibited Akt activation. Simvastatin 28-39 AKT serine/threonine kinase 1 Homo sapiens 88-91 29435052-14 2018 Furthermore, treatment with simvastatin attenuated insulin-like growth factor 1-induced Akt activation; however, the combination of simvastatin and meclofenamic acid further inhibited Akt activation. Simvastatin 28-39 AKT serine/threonine kinase 1 Homo sapiens 184-187 29435052-14 2018 Furthermore, treatment with simvastatin attenuated insulin-like growth factor 1-induced Akt activation; however, the combination of simvastatin and meclofenamic acid further inhibited Akt activation. Simvastatin 132-143 AKT serine/threonine kinase 1 Homo sapiens 184-187 29208461-0 2018 Simvastatin inhibits the development of radioresistant esophageal cancer cells by increasing the radiosensitivity and reversing EMT process via the PTEN-PI3K/AKT pathway. Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 158-161 29208461-8 2018 Mechanism assay confirmed the activation of PI3K/AKT pathway after radiation, which was inhibited by simvastatin. Simvastatin 101-112 AKT serine/threonine kinase 1 Homo sapiens 49-52 29208461-11 2018 Moreover, PTEN cessation attenuated the inhibitory effect of simvastatin on PI3K/AKT activation, and subsequently antagonized simvastatin-induced radiosensitivity and EMT reversion. Simvastatin 61-72 AKT serine/threonine kinase 1 Homo sapiens 81-84 29208461-13 2018 Together, simvastatin inhibits the development of Ec9706-R cells by increasing radiosensitivity and reversing EMT via PTEN-PI3K/AKT pathway, implying a promising strategy against EC radioresistance. Simvastatin 10-21 AKT serine/threonine kinase 1 Homo sapiens 128-131 31576676-0 2019 Simvastatin preparations promote PDGF-BB secretion to repair LPS-induced endothelial injury through the PDGFRbeta/PI3K/Akt/IQGAP1 signalling pathway. Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 119-122 31576676-12 2019 SV/SV-NPs promoted the secretion of platelet-derived growth factor-BB (PDGF-BB) and activated the PDGFRbeta/PI3K/Akt/IQGAP1 pathway. Simvastatin 0-2 AKT serine/threonine kinase 1 Homo sapiens 113-116 31576676-12 2019 SV/SV-NPs promoted the secretion of platelet-derived growth factor-BB (PDGF-BB) and activated the PDGFRbeta/PI3K/Akt/IQGAP1 pathway. Simvastatin 3-5 AKT serine/threonine kinase 1 Homo sapiens 113-116 31576676-13 2019 SV preparations restored endothelial barrier function by restoring endothelial cell migration, which is involved in the regulation of the PDGFRbeta/PI3K/Akt/IQGAP1 pathway and PDGF-BB secretion. Simvastatin 0-2 AKT serine/threonine kinase 1 Homo sapiens 153-156 31452046-6 2019 Western blot analysis revealed that Ras downstream signaling molecules including Akt, MEK, and ERK1/2 were markedly inhibited in THP1 cells compared to other AML cells when exposed to simvastatin. Simvastatin 184-195 AKT serine/threonine kinase 1 Homo sapiens 81-84 31092879-5 2019 Furthermore, simvastatin impaired the phosphorylation of Akt (Protein Kinase B) mainly at Ser473 and less at Thr308, indicating impaired activity of the mammalian Target of Rapamycin Complex 2 (mTORC2). Simvastatin 13-24 AKT serine/threonine kinase 1 Homo sapiens 57-60 31092879-10 2019 In conclusion, simvastatin impaired activation of Akt Ser473 most likely as a consequence of reduced activity of mTORC2. Simvastatin 15-26 AKT serine/threonine kinase 1 Homo sapiens 50-53 27743890-9 2016 Simvastatin also decreased phosphorylation of insulin receptor (IR), insulin receptor substrate 1 (IRS-1), AKT and glycogen synthase kinase 3beta (GSK-3beta), and downregulated GLUT4. Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 107-110 28554582-8 2017 A Rac inhibitor, and N17Rac1 dominant negative mutant, significantly induced PCSK9 levels, and a suppression of Rac1 expression by siRNA, counteract the effect of simvastatin on the induction of PCSK9 mRNA. Simvastatin 163-174 AKT serine/threonine kinase 1 Homo sapiens 2-5 28554582-9 2017 Finally, simvastatin, and Rac inhibitor inhibited the nuclear translocation of STAT3 and its knock-down by siRNA increased significantly the susceptibility of Caco-2 to simvastatin on PCSK9 expression. Simvastatin 169-180 AKT serine/threonine kinase 1 Homo sapiens 26-29 27743890-10 2016 In conclusion, our data indicate that simvastatin decreased both basal and insulin-stimulated glucose uptake through inhibiting the critical steps in IR/IRS-1/AKT signaling cascade, and by hindering GLUT4 function and normal regulation of glycogen synthesis, contributing to insulin resistance. Simvastatin 38-49 AKT serine/threonine kinase 1 Homo sapiens 159-162 27470565-5 2016 Mechanistically, the inhibition of glucose uptake and GLUT4 translocation elicited by simvastatin were associated with the suppression of the insulin receptor (IR)/IR substrate (IRS)/Akt signaling cascade. Simvastatin 86-97 AKT serine/threonine kinase 1 Homo sapiens 183-186 27779188-7 2016 Furthermore, simvastatin suppressed BCa cell metastasis by inhibiting EMT and affecting AKT/GSK3beta. Simvastatin 13-24 AKT serine/threonine kinase 1 Homo sapiens 88-91 27470565-0 2016 Simvastatin inhibits glucose uptake activity and GLUT4 translocation through suppression of the IR/IRS-1/Akt signaling in C2C12 myotubes. Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 105-108 27470565-6 2016 Simvastatin suppressed the phosphorylation of IR, IRS-1 and Akt, and total expression of IR or IRS-1, but did not affect Akt. Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 60-63 27470565-8 2016 In conclusion, our findings indicate that simvastatin suppresses glucose uptake activity and GLUT4 translocation via IR-dependent IRS-1/PI3K/Akt pathway. Simvastatin 42-53 AKT serine/threonine kinase 1 Homo sapiens 141-144 26304753-11 2015 These findings suggest that sEH phosphatase activity negatively regulates simvastatin-activated eNOS by impeding the Akt-AMPK-eNOS signaling cascade. Simvastatin 74-85 AKT serine/threonine kinase 1 Homo sapiens 117-120 27347133-6 2016 In addition, simvastatin suppressed the expression of IGF-1R and inhibited the activity of phosphorylated-extracellular signal-regulated kinase (ERK)1/2 and phosphorylated-Akt activated by IGF-1. Simvastatin 13-24 AKT serine/threonine kinase 1 Homo sapiens 172-175 27347133-10 2016 It was concluded that simvastatin induces the apoptosis of human colon cancer cells and inhibits IGF-1-induced ERK and Akt expression via the downregulation of IGF-1R expression and proapoptotic ERK activation. Simvastatin 22-33 AKT serine/threonine kinase 1 Homo sapiens 119-122 26565813-0 2016 Simvastatin-induced breast cancer cell death and deactivation of PI3K/Akt and MAPK/ERK signalling are reversed by metabolic products of the mevalonate pathway. Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 70-73 26565813-5 2016 Simvastatin markedly suppressed PI3K/Akt/mTOR signalling by activating PTEN (p = 0.005) and by dephosphorylating Akt (p = 0.002) and S6RP (p = 0.033); it also inhibited MAPK/ERK pathway by dephosphorylating c-Raf (p = 0.018) and ERK1/2 (p = 0.002). Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 37-40 26565813-5 2016 Simvastatin markedly suppressed PI3K/Akt/mTOR signalling by activating PTEN (p = 0.005) and by dephosphorylating Akt (p = 0.002) and S6RP (p = 0.033); it also inhibited MAPK/ERK pathway by dephosphorylating c-Raf (p = 0.018) and ERK1/2 (p = 0.002). Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 113-116 26565813-7 2016 Concordantly, simvastatin strongly suppressed PI3K/Akt/mTOR pathway by enhancing PTEN expression and by further sequentially dephosphorylating downstream cascades including Akt, mTOR, p70S6K, S6RP and 4E-BP1. Simvastatin 14-25 AKT serine/threonine kinase 1 Homo sapiens 51-54 26565813-7 2016 Concordantly, simvastatin strongly suppressed PI3K/Akt/mTOR pathway by enhancing PTEN expression and by further sequentially dephosphorylating downstream cascades including Akt, mTOR, p70S6K, S6RP and 4E-BP1. Simvastatin 14-25 AKT serine/threonine kinase 1 Homo sapiens 173-176 27323826-0 2016 Simvastatin induces heme oxygenase-1 via NF-E2-related factor 2 (Nrf2) activation through ERK and PI3K/Akt pathway in colon cancer. Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 103-106 27323826-9 2016 PI3K/Akt inhibitor (LY294002) and ERK inhibitor (PD98059) suppressed simvastatin-induced Nrf2 and HO-1 expression in both HT-29 and HCT 116 cells. Simvastatin 69-80 AKT serine/threonine kinase 1 Homo sapiens 5-8 27323826-10 2016 This study shows that simvastatin induces the activation and nuclear translocation of Nrf2 and the expression of various anti-oxidant enzymes via ERK and PI3K/Akt pathway in colon cancer cells. Simvastatin 22-33 AKT serine/threonine kinase 1 Homo sapiens 159-162 26470769-9 2016 Moreover, simvastatin suppressed the expression of the IGF-1 receptor and IGF-1-induced ERK/Akt activation. Simvastatin 10-21 AKT serine/threonine kinase 1 Homo sapiens 92-95 26334381-0 2015 Simvastatin protects the heart against ischemia reperfusion injury via inhibiting HMGB1 expression through PI3K/Akt signal pathways. Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 112-115 26304753-8 2015 In addition, pharmacological inhibition of sEH phosphatase or overexpressing the inactive phosphatase domain of sEH enhanced simvastatin-induced NO bioavailability, tube formation and phosphorylation of eNOS, Akt, and AMP-activated protein kinase (AMPK). Simvastatin 125-136 AKT serine/threonine kinase 1 Homo sapiens 209-212 26304753-10 2015 Simvastatin evoked epidermal growth factor receptor-c-Src-increased Tyr phosphorylation of sEH and formation of an sEH-Akt-AMPK-eNOS complex, which was abolished by the c-Src kinase inhibitor PP1 or c-Src dominant-negative mutant K298M. Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 119-122 25520153-0 2015 Synergistic Effect of Sulindac and Simvastatin on Apoptosis in Lung Cancer A549 Cells through AKT-Dependent Downregulation of Survivin. Simvastatin 35-46 AKT serine/threonine kinase 1 Homo sapiens 94-97 25520153-4 2015 MATERIALS AND METHODS: Cell viability was measured by an MTT assay, while the expression of apoptotic markers, AKT, and survivin in response to sulindac and simvastatin was examined by Western blotting. Simvastatin 157-168 AKT serine/threonine kinase 1 Homo sapiens 111-114 25520153-13 2015 CONCLUSION: Combined treatment with sulindac and simvastatin augmented their apoptotic potential in lung cancer cells through AKT signaling-dependent downregulation of survivin. Simvastatin 49-60 AKT serine/threonine kinase 1 Homo sapiens 126-129 23901824-4 2014 RESULTS: HL-1 cardiomyocytes exposed to simvastatin for 24 h exhibited diminished protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling, increased activation of unc-51-like kinase 1, and upregulation of autophagy and mitophagy. Simvastatin 40-51 AKT serine/threonine kinase 1 Homo sapiens 100-103 25122066-6 2014 Combination of simvastatin and metformin decreased Akt Ser-473 and Thr-308 phosphorylation and AMPKalpha Ser-485/491 phosphorylation; increased Thr-172 phosphorylation and AMPKalpha activity, as assessed by increased Ser-79 and Ser-872 phosphorylation of acetyl-CoA carboxylase and HMG-CoAR, respectively; decreased HMG-CoAR activity; and reduced total cellular cholesterol and its synthesis in both cell lines. Simvastatin 15-26 AKT serine/threonine kinase 1 Homo sapiens 51-54 25023790-11 2014 Simvastatin suppressed cardiac RhoA mobilization and triggered Akt/eNOS signaling. Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 63-66 24887036-8 2014 Simvastatin therapy partially reduced HDL inflammation index, improved the capacity of HDL to stimulate eNOS and Akt phosphorylation at S1177, eNOS associated with HSP90, NO production, reduced eNOS phosphorylation at T495 and superoxide generation, and improved endothelium-dependent vasodilation. Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 113-116 24880141-7 2014 The effects of simvastatin on the AKT/mTOR and MAPK pathways were determined by Western blotting. Simvastatin 15-26 AKT serine/threonine kinase 1 Homo sapiens 34-37 24880141-10 2014 Treatment with simvastatin resulted in inhibition of the MAPK pathway and exhibited differential effects on the AKT/mTOR pathway in the ECC-1 and Ishikawa cells. Simvastatin 15-26 AKT serine/threonine kinase 1 Homo sapiens 112-115 24880141-14 2014 CONCLUSION: Simvastatin had significant anti-proliferative and anti-metastatic effects in endometrial cancer cells, possibly through modulation of the MAPK and AKT/mTOR pathways, suggesting that statins may be a promising treatment strategy for endometrial cancer. Simvastatin 12-23 AKT serine/threonine kinase 1 Homo sapiens 160-163 23947572-9 2013 Simvastatin, but not atorvastatin, inhibited the activity of prosurvival serine-threonine kinase Akt and induced marked up-regulation of cleaved caspase-3, a marker of cell apoptosis. Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 97-100 24631288-5 2014 Simvastatin also strongly inhibited AKT activation, leading to suppression of beta-catenin activity and the expression of its targets, survivin and cyclin D1. Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 36-39 24631288-6 2014 Both insulin treatment and AKT overexpression markedly increased p-beta-catenin and survivin levels, even in the presence of gefitinib and simvastatin. Simvastatin 139-150 AKT serine/threonine kinase 1 Homo sapiens 27-30 24631288-11 2014 Overall, these data indicate that simvastatin may overcome EGFR-TKI resistance in T790M mutant NSCLCs via an AKT/beta-catenin signaling-dependent down-regulation of survivin and apoptosis induction. Simvastatin 34-45 AKT serine/threonine kinase 1 Homo sapiens 109-112 23690956-0 2013 Simvastatin inhibits renal cancer cell growth and metastasis via AKT/mTOR, ERK and JAK2/STAT3 pathway. Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 65-68 23603515-8 2013 Simvastatin, an inhibitor of cholesterol synthesis, also abrogated rituximab-mediated Syk and Akt activation. Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 94-97 23973711-9 2013 The TNBC cell lines, which showed increased expression of p-Akt, appeared to attenuate the expression of p-Akt by PTEN loss in simvastatin-treated TNBC cells. Simvastatin 127-138 AKT serine/threonine kinase 1 Homo sapiens 60-63 23973711-9 2013 The TNBC cell lines, which showed increased expression of p-Akt, appeared to attenuate the expression of p-Akt by PTEN loss in simvastatin-treated TNBC cells. Simvastatin 127-138 AKT serine/threonine kinase 1 Homo sapiens 107-110 23973711-10 2013 The Akt inhibitor, LY294002, augmented the effect of simvastatin on PTEN wild-type TNBC cells. Simvastatin 53-64 AKT serine/threonine kinase 1 Homo sapiens 4-7 23690956-7 2013 Mechanically, we presented that simvastatin could suppress the proliferation and motility of RCC cells via inhibiting the phosphorylation of AKT, mTOR, and ERK in a time- and dose- dependent manner. Simvastatin 32-43 AKT serine/threonine kinase 1 Homo sapiens 141-144 23690956-9 2013 In conclusion, these findings suggested that simvastatin-induced apoptosis and its anti-metastasis activity in RCC cells were accompanied by inhibition of AKT/mTOR, ERK, and JAK2/STAT3 pathways, which imply that simvastatin may be a potential therapeutic agent for the treatment of RCC patients. Simvastatin 45-56 AKT serine/threonine kinase 1 Homo sapiens 155-158 22796581-9 2012 Simvastatin increased NO production, the expression of eNOS and phosphorylation at serine1177, phosphorylation of Akt, expression of heat shock protein 90, heat shock protein 90 association with eNOS and decreased eNOS phosphorylation at threonine 495, phosphorylation of p38, and expression of caveolin-1. Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 114-117 23026078-12 2012 Simvastatin activated Akt and mTOR, inactivated GSK-3beta and dephosphorylated APC in the injured PCNs. Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 22-25 23026078-14 2012 The beneficial effects of simvastatin on neurite outgrowth may be mediated through manipulation of the PI-3K/Akt/mTOR and PI-3K/GSK-3beta/APC pathways. Simvastatin 26-37 AKT serine/threonine kinase 1 Homo sapiens 109-112 22918643-10 2012 Simvastatin-dependent HO-1 protein induction was reduced significantly by pharmacological inhibition of the phosphotidylinositol-3-kinase (PI3K)/Akt pathways. Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 145-148 22918643-13 2012 Simvastatin-dependent upregulation of HO-1 is mainly via PI3K/Akt-dependent signaling pathways. Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 62-65 22974127-6 2012 Protein expression of major candidates of the intrinsic pathway downstream of simvastatin-mediated Akt inactivation was analyzed. Simvastatin 78-89 AKT serine/threonine kinase 1 Homo sapiens 99-102 20946258-0 2012 Simvastatin inhibits glucose-stimulated vascular smooth muscle cell migration involving increased expression of RhoB and a block of Ras/Akt signal. Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 136-139 20946258-6 2012 RESULTS: Under high glucose conditions, simvastatin dose-dependently inhibited VSMC migration, decreased PI3K/Akt pathway activity, reduced c-Raf and Ras expression, increased RhoB but not RhoA, Rac1, and Cdc2 expression, dose-dependently inhibited MMP-2, but not MMP-9, activity, and dose-dependently inhibited NF-kappaB activity. Simvastatin 40-51 AKT serine/threonine kinase 1 Homo sapiens 110-113 22541079-0 2012 [Effects of simvastatin on PI3K/AKT signaling pathway in human acute monocytic leukemia cell line SHI-1]. Simvastatin 12-23 AKT serine/threonine kinase 1 Homo sapiens 32-35 21839782-10 2011 These results suggest that disruption of Igf-1/Akt signaling is a causative factor in simvastatin-induced mitochondrial dysfunction in C2C12 myotubes, whereas HepG2 cells are protected by maintaining Igf-1/Akt signaling. Simvastatin 86-97 AKT serine/threonine kinase 1 Homo sapiens 206-209 21871960-7 2012 Simvastatin induced the activation of AMP-activated protein kinase (AMPK) and its target Raptor, while simultaneously downregulating activation of Akt. Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 147-150 21871960-8 2012 Mammalian target of rapamycin (mTOR), a major AMPK/Akt downstream target and a major negative autophagy regulator, and its substrate p70 S6 kinase 1 were also inhibited by simvastatin. Simvastatin 172-183 AKT serine/threonine kinase 1 Homo sapiens 51-54 21395587-15 2011 During cell spreading, simvastatin diminished Rac activation. Simvastatin 23-34 AKT serine/threonine kinase 1 Homo sapiens 46-49 20464445-0 2011 Apoptotic induction by simvastatin in human lung cancer A549 cells via Akt signaling dependent down-regulation of survivin. Simvastatin 23-34 AKT serine/threonine kinase 1 Homo sapiens 71-74 20464445-5 2011 Simvastatin also resulted in a decrease in the expression of phosphorylated Akt. Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 76-79 20464445-10 2011 Taken together, these data suggest that the anti-cancer effect of simvastatin via induction of apoptosis is related to Akt signaling dependent down-regulation of survivin in lung cancer A549 cells. Simvastatin 66-77 AKT serine/threonine kinase 1 Homo sapiens 119-122 21059805-0 2011 Anticancer efficacy of simvastatin on prostate cancer cells and tumor xenografts is associated with inhibition of Akt and reduced prostate-specific antigen expression. Simvastatin 23-34 AKT serine/threonine kinase 1 Homo sapiens 114-117 21059805-5 2011 In the current study, we sought to investigate the effects of simvastatin on the Akt pathway in prostate cancer cells with respect to the regulation of various cell functions in vitro and tumor growth in vivo. Simvastatin 62-73 AKT serine/threonine kinase 1 Homo sapiens 81-84 21059805-6 2011 Time- and dose-dependent effects of simvastatin on LNCaP (androgen-dependent) and PC3 (androgen-independent) cells indicate that treatment with simvastatin at concentrations as low as 25 muM was sufficient to inhibit serum-stimulated Akt activity. Simvastatin 144-155 AKT serine/threonine kinase 1 Homo sapiens 234-237 21059805-8 2011 Simvastatin-mediated effects on colony formation were rescued by adenovirus-mediated expression of constitutively active Akt (myristoylated Akt) in PC3 cell lines. Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 121-124 21059805-8 2011 Simvastatin-mediated effects on colony formation were rescued by adenovirus-mediated expression of constitutively active Akt (myristoylated Akt) in PC3 cell lines. Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 140-143 21059805-10 2011 Our findings demonstrate the therapeutic benefits of simvastatin for prostate cancer and suggest a link between simvastatin, regulation of Akt activity, and PSA expression in prostate tumors. Simvastatin 112-123 AKT serine/threonine kinase 1 Homo sapiens 139-142 16825658-4 2006 Although the mechanisms involved are unclear, we previously identified activation of the small GTPase Rac and translocation of cortactin, an actin-binding protein, as key to EC barrier augmentation induced by simvastatin and sphingosine 1-phosphate and therefore examined the role of these molecules in ATP-induced EC barrier enhancement. Simvastatin 209-220 AKT serine/threonine kinase 1 Homo sapiens 102-105 20060890-4 2010 We demonstrate that in the tumors derived from MDA-MB-231 human breast cancer cell xenografts, simvastatin significantly inhibited phosphorylation of Akt with concomitant attenuation of the expression of the anti-apoptotic protein Bcl(XL). Simvastatin 95-106 AKT serine/threonine kinase 1 Homo sapiens 150-153 19934968-8 2009 Simvastatin induced an increase of caspase-3 activity and annexin V staining, and down-regulated the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 138-141 19934968-9 2009 Simvastatin also decreased cholesterol content in lipid raft fractions, suppressed caveolin-1 expression in the lipid rafts, and induced Fas translocation into lipid rafts, suggesting that simvastatin may inhibit the prosurvival PI3K/Akt pathway and trigger caspase-3-dependent apoptotic cell death through the modulation of lipid rafts. Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 234-237 19934968-9 2009 Simvastatin also decreased cholesterol content in lipid raft fractions, suppressed caveolin-1 expression in the lipid rafts, and induced Fas translocation into lipid rafts, suggesting that simvastatin may inhibit the prosurvival PI3K/Akt pathway and trigger caspase-3-dependent apoptotic cell death through the modulation of lipid rafts. Simvastatin 189-200 AKT serine/threonine kinase 1 Homo sapiens 234-237 19934968-10 2009 CONCLUSION: These results suggest that modulation of lipid rafts, Fas translocation, and PI3K/Akt/caspase-3 pathway are involved in the antitumor effect of simvastatin and may have a potential role in cancer prevention and treatment. Simvastatin 156-167 AKT serine/threonine kinase 1 Homo sapiens 94-97 19513607-7 2009 Further study found that simvastatin raised phosphorylation levels of Akt and AMPK, and such effect could be antagonized by Akt inhibitor or AMPK inhibitor. Simvastatin 25-36 AKT serine/threonine kinase 1 Homo sapiens 70-73 19513607-7 2009 Further study found that simvastatin raised phosphorylation levels of Akt and AMPK, and such effect could be antagonized by Akt inhibitor or AMPK inhibitor. Simvastatin 25-36 AKT serine/threonine kinase 1 Homo sapiens 124-127 19513607-8 2009 These results suggest that simvastatin could stimulate the activity of eNOS via its phosphorylation by Akt and AMPK, which provides a new mechanism, other than lipid-lowering effect, for the cardiovascular protection of statins. Simvastatin 27-38 AKT serine/threonine kinase 1 Homo sapiens 103-106 19001041-8 2009 Simvastatin down-regulated PI3k/Akt signalling, independently of RhoA, and up-regulated FOXO transcription factors and downstream gene targets known to be implicated in proteasomal- and lysosomal-mediated muscle proteolysis, carbohydrate oxidation, oxidative stress and inflammation in an in vivo model of statin-induced myopathy. Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 32-35 18612412-11 2008 We also demonstrated that the pro-vascular repair mechanism of simvastatin involves VEGF stimulation, Akt phosphorylation, and nitric oxide production; and the anti-vascular repair mechanism is driven by marked intracellular cholesterol depletion and related disorganisation of key intracellular structures. Simvastatin 63-74 AKT serine/threonine kinase 1 Homo sapiens 102-105 18371146-13 2008 Simvastatin inhibited activation of extracellular signal-regulated kinase (ERK) and protein kinase B (Akt) but not c-Jun NH(2)-terminal kinase or p38 mitogen-activated protein (MAP) kinase. Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 102-105 17172275-10 2007 Simvastatin, a 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor, which is known to activate PI3K/Akt, blocks TNF-alpha- and insulin-induced PAI-1 expression. Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 99-102 20614159-7 2010 SIM interacts with PI3K/Akt and ERK1/2 signaling pathways thereby decreasing the serum withdrawal-enhanced levels of the CDK inhibitor p21(Cip1) (p21) and restoring the vulnerability of AD cells to trophic factor deprivation. Simvastatin 0-3 AKT serine/threonine kinase 1 Homo sapiens 24-27 20594940-4 2010 Simvastatin-dependent HO-1 gene activation was significantly reduced by pharmacological inhibition of the p38 MAPK and phosphotidylinositol-3-kinase (PI3K)/Akt pathways. Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 156-159 20671065-7 2010 Simvastatin, which inhibited ABCA1 expression in PC-3 and DU145 cells, attenuated HDL-induced PC-3 and DU145 cell proliferation, migration, and ERK1/2 and Akt phosphorylation. Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 155-158 20562903-0 2010 Simvastatin combined with nifedipine enhances endothelial cell protection by inhibiting ROS generation and activating Akt phosphorylation. Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 118-121 18976673-8 2008 However, simvastatin inhibited this promotion (2.5+/-0.3 mm, p<0.001 vs. TNF-alpha alone) by decreasing oxidative stress, VEGF, Akt, and eNOS. Simvastatin 9-20 AKT serine/threonine kinase 1 Homo sapiens 131-134 18489904-8 2008 Simvastatin also inhibited IGF-1-induced activation of both ERK and Akt signaling and IGF-1-induced PC-3 cell proliferation. Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 68-71 16968805-11 2006 Simvastatin therapy significantly decreased nuclear factor-kappaB and increased Akt activity in MS subjects compared with placebo. Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 80-83 12438947-0 2002 Simvastatin induces activation of the serine-threonine protein kinase AKT and increases survival of isolated human pancreatic islets. Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 70-73 14732356-0 2004 Simvastatin suppresses LPS-induced Akt phosphorylation in the human monocyte cell line THP-1. Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 35-38 14732356-12 2004 Akt phosphorylation peaked after 15 min of LPS stimulation and was suppressed by pretreatment with simvastatin. Simvastatin 99-110 AKT serine/threonine kinase 1 Homo sapiens 0-3 14732356-13 2004 CONCLUSIONS: These data demonstrate that LPS stimulation leads to increased Akt phosphorylation, which can be suppressed with simvastatin pretreatment. Simvastatin 126-137 AKT serine/threonine kinase 1 Homo sapiens 76-79 15843472-5 2005 Moreover, three different statins, mevastatin, pravastatin, and simvastatin, inhibited in a dose-dependent manner apoptosis and loss of nephrin induced by oxLDL by stimulating Akt activity. Simvastatin 64-75 AKT serine/threonine kinase 1 Homo sapiens 176-179 15776112-3 2005 Simvastatin, a cholesterol synthesis inhibitor, lowered raft cholesterol content, inhibited Akt1 serine-threonine kinase (protein kinase Balpha)/protein kinase B (Akt/PKB) pathway signaling, and induced apoptosis in caveolin- and PTEN-negative LNCaP PCa cells. Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 92-96 15776112-3 2005 Simvastatin, a cholesterol synthesis inhibitor, lowered raft cholesterol content, inhibited Akt1 serine-threonine kinase (protein kinase Balpha)/protein kinase B (Akt/PKB) pathway signaling, and induced apoptosis in caveolin- and PTEN-negative LNCaP PCa cells. Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 163-170 15337692-9 2004 Simvastatin activated p38 and Akt in VSMCs, and the respective inhibitors of p38 and phosphoinositide 3-kinase (PI3K) greatly reduced the level of simvastatin-induced HO-1, which suggests the involvement of p38 and the PI3K-Akt pathway in HO-1 induction. Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 224-227 15337692-9 2004 Simvastatin activated p38 and Akt in VSMCs, and the respective inhibitors of p38 and phosphoinositide 3-kinase (PI3K) greatly reduced the level of simvastatin-induced HO-1, which suggests the involvement of p38 and the PI3K-Akt pathway in HO-1 induction. Simvastatin 147-158 AKT serine/threonine kinase 1 Homo sapiens 30-33 15337692-9 2004 Simvastatin activated p38 and Akt in VSMCs, and the respective inhibitors of p38 and phosphoinositide 3-kinase (PI3K) greatly reduced the level of simvastatin-induced HO-1, which suggests the involvement of p38 and the PI3K-Akt pathway in HO-1 induction. Simvastatin 147-158 AKT serine/threonine kinase 1 Homo sapiens 224-227 14988829-2 2004 We hypothesized that simvastatin, which enhances Akt-dependent endothelial nitric oxide synthase phosphorylation, may increase hepatic nitric oxide release and decrease hepatic resistance in patients with cirrhosis and portal hypertension. Simvastatin 21-32 AKT serine/threonine kinase 1 Homo sapiens 49-52 12438947-4 2002 Simvastatin activates Akt in mammalian cells; therefore, we investigated the role of simvastatin on human pancreatic islets (HPI) survival. Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 22-25 12438947-11 2002 Akt activation; increase in islet viability; and decrease in Bad phosphorylation, cytochrome release, caspase-9 activation, and translocation of FKHR were observed after simvastatin treatment, effects reversed by LY294002. Simvastatin 170-181 AKT serine/threonine kinase 1 Homo sapiens 0-3 11863404-1 2002 Recent studies suggest that the HMG-CoA reductase inhibitor simvastatin--similar to vascular endothelial growth factor (VEGF)--may promote angiogenesis by activation of a protein kinase Akt-nitric oxide synthase dependent pathway in endothelial cells, an effect that may be beneficial in the treatment of ischemic heart disease. Simvastatin 60-71 AKT serine/threonine kinase 1 Homo sapiens 186-189 11956113-13 2002 Akt dephosphorylation by thrombin was blocked by both simvastatin and Y-27632. Simvastatin 54-65 AKT serine/threonine kinase 1 Homo sapiens 0-3 11956113-15 2002 Simvastatin prevents its induction through inhibition of Rho/Rho-kinase and activation of Akt. Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 90-93 34799978-0 2021 Simvastatin treatment promotes proliferation of human dental pulp stem cells via modulating PI3K/AKT/miR-9/KLF5 signalling pathway. Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 97-100 34843676-0 2021 Simvastatin potentiates the cell-killing activity of imatinib in imatinib-resistant chronic myeloid leukemia cells mainly through PI3K/AKT pathway attenuation and Myc downregulation. Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 135-138 34843676-8 2021 Mechanistically, the cooperative interaction of simvastatin and imatinib was associated with the inactivation of the PI3K/Akt signaling pathway, which was a classical downstream pro-survival cascade of the BCR-ABL kinase. Simvastatin 48-59 AKT serine/threonine kinase 1 Homo sapiens 122-125 34799978-2 2021 First, western-blot and real-time quantitative PCR were used to detect the effect of simvastatin or LY294002 on the expression levels of AKT, miR-9 and KLF5, or determine the effect of miR-9. Simvastatin 85-96 AKT serine/threonine kinase 1 Homo sapiens 137-140 34799978-3 2021 Simvastatin, KLF5 and AKT significantly enhanced the proliferation of pulp stem cells, whilst this effect induced by simvastatin was suppressed by LY294002, AKT siRNA, KLF5 siRNA and miR-9, and simvastatin dose-dependently upregulated the expression of PI3K. Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 157-160 34799978-3 2021 Simvastatin, KLF5 and AKT significantly enhanced the proliferation of pulp stem cells, whilst this effect induced by simvastatin was suppressed by LY294002, AKT siRNA, KLF5 siRNA and miR-9, and simvastatin dose-dependently upregulated the expression of PI3K. Simvastatin 117-128 AKT serine/threonine kinase 1 Homo sapiens 22-25 34799978-3 2021 Simvastatin, KLF5 and AKT significantly enhanced the proliferation of pulp stem cells, whilst this effect induced by simvastatin was suppressed by LY294002, AKT siRNA, KLF5 siRNA and miR-9, and simvastatin dose-dependently upregulated the expression of PI3K. Simvastatin 117-128 AKT serine/threonine kinase 1 Homo sapiens 157-160 34799978-3 2021 Simvastatin, KLF5 and AKT significantly enhanced the proliferation of pulp stem cells, whilst this effect induced by simvastatin was suppressed by LY294002, AKT siRNA, KLF5 siRNA and miR-9, and simvastatin dose-dependently upregulated the expression of PI3K. Simvastatin 194-205 AKT serine/threonine kinase 1 Homo sapiens 22-25 34799978-4 2021 Furthermore, simvastatin upregulated PI3K and p-AKT expression in a concentration-dependent manner. Simvastatin 13-24 AKT serine/threonine kinase 1 Homo sapiens 48-51 34799978-5 2021 LY294002 abrogated the upregulation of p-AKT expression levels induced by simvastatin, and LY294002 induced the miR-9 expression and simvastatin dose-dependently inhibited the expression of miR-9, by contrast, LY294002 reduced the KLF5 expression and simvastatin dose-dependently promoted the expression of KLF5. Simvastatin 74-85 AKT serine/threonine kinase 1 Homo sapiens 41-44 34799978-8 2021 These findings suggested simvastatin could promote the proliferation of pulp stem cells, possibly by suppressing the expression of miR-9 via activating the PI3K/AKT signalling pathway, and the downregulation of miR-9 upregulated the expression of its target gene, KLF5, which is directly responsible for the enhanced proliferation of pulp stem cells. Simvastatin 25-36 AKT serine/threonine kinase 1 Homo sapiens 161-164 33295884-6 2020 Phosphorylation of insulin signalling targets Akt substrate 160 kDa (AS160) and glycogen synthase kinase 3beta (GSK3beta) was upregulated with lactone-, but not with acid-form simvastatin. Simvastatin 176-187 AKT serine/threonine kinase 1 Homo sapiens 46-49 34461224-10 2021 Simvastatin also inhibited E2 downstream signaling, including ERK and AKT pathways, E2/ER transcriptional activity and E2-responsive genes. Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 70-73 34111424-7 2021 Simvastatin impaired the phosphorylation of the insulin receptor (IR beta), Akt ser473 and S6rp, and increased phosphorylation of AMPK thr172 in both myotubes and myoblasts, which was prevented by insulin and mevalonate. Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 76-79 33042440-0 2020 Simvastatin ameliorates oxygen glucose deprivation/reoxygenation-induced pulmonary endothelial barrier dysfunction by restoring cell-cell junctions and actin cytoskeleton dynamics via the PI3K/Akt signaling pathway. Simvastatin 0-11 AKT serine/threonine kinase 1 Homo sapiens 193-196 32172201-5 2020 It is revealed that Simvastatin can potentially interact with certain known targets or key regulators of GBM such as ErbB, c-Src and FGFR signaling pathways, but exhibit low affinity to the well-established GBM target of PI3K/Akt/mTOR pathway. Simvastatin 20-31 AKT serine/threonine kinase 1 Homo sapiens 226-229