PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 18337644-11 2008 Consistent with the cell cycle arrest, simvastatin caused an increase in the mRNA levels of p21 and p27 on G361 and MMAc cells. Simvastatin 39-50 H3 histone pseudogene 16 Homo sapiens 92-95 17428261-6 2007 The inhibitory effect of simvastatin on cell proliferation seemed to be associated with cell cycle arrest and increased expression of p21, p27, and activated caspase-3. Simvastatin 25-36 H3 histone pseudogene 16 Homo sapiens 134-137 29113274-10 2017 Additionally, simvastatin in combination with doxorubicin significantly induced expression of the cyclin-dependent kinase inhibitor p21, increased cytochrome c and caspase 3 expression and reduced cyclin D1 expression. Simvastatin 14-25 H3 histone pseudogene 16 Homo sapiens 132-135 32633363-10 2020 Meanwhile, simvastatin treatment caused cell cycle arrest in G0/G1 phase, remarkably downregulated expression of cyclin D1, and upregulated expressions of p21 and Bim. Simvastatin 11-22 H3 histone pseudogene 16 Homo sapiens 155-158 16985065-9 2006 All three statins (lovastatin, fluvastatin, and simvastatin) inhibited cyclin E/cdk2 kinase leading to hypophosphorylation of Rb, but this inhibition was correlated with a loss of the activating phosphorylation on Thr160 of cyclin E-associated cdk2 and not dependent on the cdk inhibitors p21 and p27. Simvastatin 48-59 H3 histone pseudogene 16 Homo sapiens 289-292 31752013-11 2019 Simvastatin disrupted this senescence mechanism via the miR-155/SIRT1/FoxO-1/p21 pathway signaling. Simvastatin 0-11 H3 histone pseudogene 16 Homo sapiens 77-80 28230855-0 2017 Simvastatin-induced cell cycle arrest through inhibition of STAT3/SKP2 axis and activation of AMPK to promote p27 and p21 accumulation in hepatocellular carcinoma cells. Simvastatin 0-11 H3 histone pseudogene 16 Homo sapiens 118-121 28230855-5 2017 In this study, we demonstrated simvastatin-induced G0/G1 arrest by inducing p21 and p27 accumulation in HepG2 and Hep3B cells. Simvastatin 31-42 H3 histone pseudogene 16 Homo sapiens 76-79 28230855-6 2017 Simvastatin also promoted AMP-activated protein kinase (AMPK) activation, which induced p21 upregulation by increasing its transcription. Simvastatin 0-11 H3 histone pseudogene 16 Homo sapiens 88-91 28230855-10 2017 Mevalonate decreased simvastatin-induced AMPK activation and rescued phospho-STAT3 and Skp2 expression in HCC cells, which resulted in the prevention of G0/G1 arrest through inhibition of p21 and p27 accumulation. Simvastatin 21-32 H3 histone pseudogene 16 Homo sapiens 188-191 28230855-12 2017 Consistently, we found that simvastatin also increased p21 and p27 expression in tumor sections by reducing Skp2 expression and inducing AMPK activation and STAT3 suppression in the same tumor tissues. Simvastatin 28-39 H3 histone pseudogene 16 Homo sapiens 55-58 28230855-13 2017 Taken together, these findings are demonstrative of the existence of a novel pathway in which simvastatin induces G0/G1 arrest by upregulating p21 and p27 by activating AMPK and inhibiting the STAT3-Skp2 axis, respectively. Simvastatin 94-105 H3 histone pseudogene 16 Homo sapiens 143-146 21059291-1 2010 OBJECTIVE: To investigate the effects of simvastatin on the proliferation, cell cycle and expression of cyclin-dependent kinase inhibitor p21 protein in human hepatocellular carcinoma (HepG2) cells in vitro. Simvastatin 41-52 H3 histone pseudogene 16 Homo sapiens 138-141 27098189-11 2016 Simvastatin enhanced the release of cytochrome c, caspase 3, and increased p21 levels, especially for the KKU-100 cells. Simvastatin 0-11 H3 histone pseudogene 16 Homo sapiens 75-78 25727911-10 2016 Furthermore, simvastatin effectively reduced the expression of p53 and p21. Simvastatin 13-24 H3 histone pseudogene 16 Homo sapiens 71-74 24535918-9 2014 Our results provide a molecular basis for the therapeutic application of simvastatin to reduce RhoA/PTEN activation, restore cytosolic levels of phosphorylated p21/p27, and induce angiogenic processes. Simvastatin 73-84 H3 histone pseudogene 16 Homo sapiens 160-163 20946258-4 2012 Our previous study has demonstrated that simvastatin inhibits VSMC proliferation in high glucose status without dyslipidemia, inducing a G0/G1 phase cell cycle growth arrest by acting on multiple steps upstream of pRb, including inhibition of CDK2/4 expression and upregulation of p53, p21, p16, and p27. Simvastatin 41-52 H3 histone pseudogene 16 Homo sapiens 286-289 23933099-0 2013 Simvastatin rises reactive oxygen species levels and induces senescence in human melanoma cells by activation of p53/p21 pathway. Simvastatin 0-11 H3 histone pseudogene 16 Homo sapiens 117-120 23933099-4 2013 Also, the main pathways leading to cell senescence were examined in simvastatin-treated human melanoma cells, and the expression levels of phospho-p53 and p21 were upregulated by simvastatin, suggesting that cell cycle regulators and DNA damage pathways are involved in the onset of senescence. Simvastatin 68-79 H3 histone pseudogene 16 Homo sapiens 155-158 23933099-4 2013 Also, the main pathways leading to cell senescence were examined in simvastatin-treated human melanoma cells, and the expression levels of phospho-p53 and p21 were upregulated by simvastatin, suggesting that cell cycle regulators and DNA damage pathways are involved in the onset of senescence. Simvastatin 179-190 H3 histone pseudogene 16 Homo sapiens 155-158 23933099-7 2013 Collectively, our results demonstrated that simvastatin can induce senescence in human melanoma cells by activation of p53/p21 pathway, and that oxidative stress may be related to this process. Simvastatin 44-55 H3 histone pseudogene 16 Homo sapiens 123-126 21059291-7 2010 Simvastatin could also increase cyclin-dependent kinase inhibitor p21 protein expression (F = 512.133, P value less than 0.001). Simvastatin 0-11 H3 histone pseudogene 16 Homo sapiens 66-69 21059291-8 2010 CONCLUSION: Simvastatin can inhibit the growth of HepG2 cells in vitro, which may be explained by its effects of enhancing cyclin-dependent kinase inhibitor p21 protein expression and arresting HepG2 cells at G0/G1 phase of cell cycle. Simvastatin 12-23 H3 histone pseudogene 16 Homo sapiens 157-160