SIRT1 expression regulates the transformation of resistant esophageal cancer cells via the epithelial-mesenchymal transition

Qin, Tiantian; Liu, Weihua; Huo, Jinxing; Li, Leilei; Zhang, Xueyan; Shi, Xiaoli; Zhou, Junfei

doi:10.1016/j.biopha.2018.04.032

Cited by 19 publications

(11 citation statements)

References 37 publications

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“…It has been shown that Epithelial-mesenchymal transition (EMT) is associated with various tumor functions including tumor cell migration, invasion, and metastasis [18][19][20]. Several researchers have shown that EMT plays an important role in ESCC [21][22][23][24][25] and is associated with the prognosis of patients [25]. Thus, the expression of E-cadherin, N-cadherin, and Snail was measured in ESCC cells following EphA5 knocked down.…”

Section: Discussionmentioning

confidence: 99%

EphA5 knockdown enhances the invasion and migration ability of esophageal squamous cell carcinoma via epithelial-mesenchymal transition through activating Wnt/β-catenin pathway

et al. 2020

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Background: The erythropoietin-producing hepatocellular (Eph) receptor A5 (EphA5) has been found to be overexpressed in some malignant tumors and is associated with disease prognosis. However, the role of EphA5 in esophageal squamous cell carcinoma (ESCC) is not clear. Methods: In the present study, we measured the expression of EphA5 in ESCC tissues and cell lines including KYSE150 and KYSE450 cells. siRNA transfection was used to interfere with EphA5 expression in ESCC cell lines. Cell viability, colony formation, scratch and invasion assays were performed to explore the roles of EphA5 in ESCC cell lines. Flow cytometry analysis was performed to investigate whether EphA5 could affect the cell apoptosis and cycle. The biomarkers related to epithelial-mesenchymal transition (EMT) and molecules associated with Wnt/β-catenin signaling were also measured by western blot and immunofluorescence. Results: The protein and mRNA expression of EphA5 were significantly higher in fresh ESCC tissues and cell lines compared with normal control groups and human normal esophageal epithelial cells (HEEC). The cell viability assay and colony formation assay revealed that EphA5 knockdown enhanced the proliferation of KYSE150 and KYSE450 cells in vitro. The invasion and migration of ESCC cells were accelerated after EphA5 knockdown. The expression of EMT biomarkers was altered in ESCC cells transfected with siRNA targeting EphA5. Moreover, EphA5 downregulation enhanced the protein levels of β-catenin and p-GSK-3β Ser9 , which play a key role in the Wnt/β-catenin pathway. Conclusions: EphA5 knockdown promotes the proliferation of esophageal squamous cell carcinoma,enhances invasion and migration ability via epithelial-mesenchymal transition through activating Wnt/β-catenin pathway.

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Section: Discussionmentioning

confidence: 99%

EphA5 knockdown enhances the invasion and migration ability of esophageal squamous cell carcinoma via epithelial-mesenchymal transition through activating Wnt/β-catenin pathway

et al. 2020

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“…Compared with the wild-type mice, SIRT1-knockout mice had larger infarct volumes following permanent focal ischemia (Hernández-Jiménez et al, 2013), and in contrast, mice with SIRT1 overexpression showed less hippocampal damage after bilateral common carotid artery occlusion (BCAO) (Hellberg et al, 2010). Furthermore, EX527 is a specific inhibitor of SIRT1 (Qin et al, 2018). In the present study, MCAO rats were treated with BHD in the presence or absence of EX527.…”

Section: Discussionmentioning

confidence: 99%

Buyang Huanwu Decoction Targets SIRT1/VEGF Pathway to Promote Angiogenesis After Cerebral Ischemia/Reperfusion Injury

Zheng

Shan

et al. 2018

Front. Neurosci.

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Background: Ischemia stroke is known as the major cause of morbidity and mortality. Buyang Huanwu Decoction (BHD), a classical traditional Chinese medicine (TCM) formula, has been used to prevent and treat stoke for hundreds of years. The purpose of present study is to investigate the effects of BHD on angiogenesis in rats after cerebral ischemia/reperfusion (I/R) injury targeting Silent information regulator 1 (SIRT1) / Vascular endothelial growth factor (VEGF) pathway.Methods: The cerebral I/R injury model was induced by middle cerebral artery occlusion (MCAO). Adult Sprag-Dawley (SD) rats were randomly divided into five groups: sham group, normal saline (NS) group, BHD group, BHD+EX527 (SIRT1 specific inhibitor) group, and NS+EX527 group. Each group was divided into the subgroups according to 1, 3, 7, or 14 days time-point after cerebral ischemia/reperfusion, respectively. Neurological function score (NFS) was evaluated by the Rogers scale; microvascular density (MVD) in brain tissue around infarction area was observed by immunofluorescence; and the expression of SIRT1 and VEGF was assessed by Western Blot and Quantitative Real-time-PCR.Results: BHD can significantly improve NFS (P < 0.05), increase the MVD in the boundary ischemic area (P < 0.01) and elevate the expression of protein and mRNA of SIRT1 and VEGF following I/R injury (P < 0.01). In contrast, treatment with EX527 reversed the BHD-induced improvements in NFS (P < 0.01) and decreased the MVD (P < 0.01) and the expression of SIRT1 and VEGF (P < 0.05).Conclusion: BHD exerts neuroprotection targeting angiogenesis through the up-regulation of SIRT1/VEGF pathway against cerebral ischemic injury in rats.

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“…EX-527 was shown to improve the efficiency of cytotoxic agents on cancer cells, with several chemotherapeutic and genotoxic agents 40,42,60 . However, in few cases, EX-527 administered alone increased cell proliferation of cancer cell lines 49,71 . The conclusion of one of these studies on the role of SIRT1 in cancer cells is a simple summary of these apparently contradictory results:…”

Section: Cellular Assays Of Ex-527mentioning

confidence: 98%

“…Binding parameters of EX-527 with sirtuins. (EMT) in chemotherapy resistant oesophageal cancer cells 71 . Overall, several factors are important to consider to understand the effect of EX-527 on cancer cells: (i) the type of cell line and the cancer stage, from benign to advanced, (ii) the presence of other agents, conventional chemotherapy, or additional HDAC inhibitors for example, and (iii) the dose, because at higher doses (ex.…”

Section: Cellular Assays Of Ex-527mentioning

confidence: 99%

Biochemical mechanism and biological effects of the inhibition of silent information regulator 1 (SIRT1) by EX-527 (SEN0014196 or selisistat)

Broussy

Laaroussi

Vidal

2020

Journal of Enzyme Inhibition and Medicinal Chemistry

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The human sirtuin silent information regulator 1 (SIRT1) is a NAD þ-dependent deacetylase enzyme. It deacetylates many protein substrates, including histones and transcription factors, thereby controlling many physiological and pathological processes. Several synthetic inhibitors and activators of SIRT1 have been developed, and some therapeutic applications have been explored. The indole EX-527 and its derivatives are among the most potent and selective SIRT1 inhibitors. EX-527 has been often used as a pharmacological tool to explore the effect of SIRT1 inhibition in various cell types. Its therapeutic potential has, therefore, been evaluated in animal models for several pathologies, including cancer. It has also been tested in phase II clinical trial for the treatment of Huntington's disease (HD). In this review, we will provide an overview of the literature on EX-527, including its mechanism of inhibition and biological studies.

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SIRT1 expression regulates the transformation of resistant esophageal cancer cells via the epithelial-mesenchymal transition

Cited by 19 publications

References 37 publications

EphA5 knockdown enhances the invasion and migration ability of esophageal squamous cell carcinoma via epithelial-mesenchymal transition through activating Wnt/β-catenin pathway

EphA5 knockdown enhances the invasion and migration ability of esophageal squamous cell carcinoma via epithelial-mesenchymal transition through activating Wnt/β-catenin pathway

Buyang Huanwu Decoction Targets SIRT1/VEGF Pathway to Promote Angiogenesis After Cerebral Ischemia/Reperfusion Injury

Biochemical mechanism and biological effects of the inhibition of silent information regulator 1 (SIRT1) by EX-527 (SEN0014196 or selisistat)

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