scholarly journals mTOR Inhibitor PP242 Increases Antitumor Activity of Sulforaphane by Blocking Akt/mTOR Pathway in Esophageal Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Zhaoming Lu ◽  
Yalin Zhang ◽  
Yujia Xu ◽  
Huiyun Wei ◽  
Wen Zhao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Molecular Mechanism ◽  
Squamous Cell ◽  
Cell Cycle Phase ◽  
Mtor Pathway ◽  
Cycle Phase ◽  
Anti Tumor Activity

Abstract This study aims to explore the anti-tumor activity of Sulforaphane (SFN) alone and combined with Akt/mTOR pathway inhibitors as well as the potential molecular mechanism in esophageal squamous cell carcinoma (ESCC). MTT assay, clone formation experiment, wound healing assays, flow cytometry, Western blot and xenograft experiment were used to test the effects and molecular mechanism of SFN alone or combined with Akt/mTOR inhibitors on proliferation, migration, cell cycle phase, apoptosis of ESCC cells and tumor growth, respectively. The results showed that SFN significantly inhibited the viability and induced apoptosis of ECa109 and EC9706 cells in a dose-dependent manner by increasing the expression of the apoptotic proteins Cleaved-caspase 9. SFN combined with PP242, but not MK2206 and RAD001, had synergetic inhibition effects on the proliferation of ESCC cells. Moreover, the combination of SFN and PP242 had better inhibiting efficiency on clone formation, migratory, cell cycle phase and the growth of xenografts of ESCC cells, as well as the more powerful apoptosis-inducing effects on ESCC cells. Results of protein expression showed that PP242 abrogated the promotion effects of SFN on p-p70S6K (Thr389) and p-Akt (Ser473). These foundings demonstrated PP242 enhances the anti-tumor activity of SFN by blocking the activation of Akt/mTOR pathway by SFN in ESCC.

scholarly journals MicroRNA-527 Induces Proliferation and Cell Cycle in Esophageal Squamous Cell Carcinoma Cells by Repressing PH Domain Leucine-Rich-Repeats Protein Phosphatase 2

Dose-Response ◽  
2020 ◽  
Vol 18 (2) ◽  
pp. 155932582092868 ◽  
Author(s):  
Qingjie Xian ◽  
Ronglei Zhao ◽  
Juanjuan Fu
Keyword(s):  
Cell Cycle ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Progression ◽  
Squamous Cell ◽  
Protein Phosphatase ◽  
Ph Domain ◽  
Gene Reporter Assay ◽  
Protein Phosphatase 2

Increasing evidence indicated that microRNAs served dominant roles in carcinogenesis and cancer progression by targeting potential downstream genes. In our study, we found that miR-527 was an upregulated expression in human esophageal squamous cell carcinoma (ESCC) cells and tissues. Furthermore, overexpression of miR-527 promoted cell proliferation and colony formation, enhanced anchorage-independent growth ability, and contributed to cell cycle. In addition, protein phosphatase 2 (PHLPP2) was identified as the direct downstream target gene of miR-527 and was confirmed by luciferase gene reporter assay. In summary, we concluded that miR-527 acted as an oncogenic microRNA in ESCC development by directly targeting PHLPP2 might be a novel therapeutic target for the treatment of ESCC.

scholarly journals Casticin treatment inhibits squamous cell carcinoma cell proliferation and arrests cell cycle in S phase

2016 ◽  
Vol 11 (1) ◽  
pp. 206 ◽  
Author(s):  
Yong-Bin Song ◽  
Shao-Hui Zhou ◽  
Hong-Shang Cui ◽  
Hui-Ning Liu ◽  
Li-Jun Liu
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Squamous Cell ◽  
Carcinoma Cell ◽  
Squamous Cell Carcinoma Cell ◽  
Carcinoma Cell Lines

<p class="Abstract">The present study demonstrates the effect of casticin on esophageal squamous cell carcinoma cell lines, TE-1 and TE-15. The cells were treated with various concentrations (10-50 μM) of casticin for different time periods. The results revealed that casticin treatment significantly inhibited the rate of cell proliferation in both TE-1 and TE-15 cell lines after 48 hours. Casticin treatment induced cell cycle arrest in S phase, enhanced the expression of proapoptotic gene, Bax and activation of caspase-3. Moreover, the morphological features of the cells were altered resulting in apoptosis. Casticin also inhibited the migration potential of TE-1 cells. Thus, casticin exhibits inhibitory effect on the esophageal squamous cell carcinoma cell lines by inhibiting cell proliferation, arresting cell cycle, inducing apoptosis and inhibiting migration. Therefore, casticin can be of therapeutic importance for the treatment of esophageal squamous cell carcinoma.</p><p> </p>

Circ_DLG1 facilitates esophageal squamous cell carcinoma progression by mediating miR-338-3p/MAP3K9 axis via activating MAPK/ERK pathway

2020 ◽  
Author(s):  
Yixuan Yang ◽  
Bing Zhu ◽  
Zhaofeng Ning ◽  
Xiaodong Wang ◽  
Zhaoxia Li ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Mitogen Activated Protein Kinase ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Erk Pathway

Abstract Background: Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy with a high incidence and poor prognosis. The document of circular RNAs (circRNAs) is frequently associated with cancer development. This study intended to explore the functional mechanism of circ_DLG1 in ESCC.Methods: The expression of circ_DLG1, miR-338-3p and Mitogen-Activated Protein Kinase Kinase Kinase 9 (MAP3K9) was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell cycle, proliferation, migration and invasion were performed for functional analysis using flow cytometry, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and transwell assay, respectively. The protein levels of MAP3K9, p38, phosphor p38 (p-p38), ERK1/2, phosphor ERK1/2 (p-ERK1/2) were detected by western blot. Bioinformatics tool for target prediction used the online tool starBase. Dual-luciferase reporter assay was performed to verify the target relationship. The animal experiments were performed to ascertain the role of circ_DLG1 in vivo.Results: The expression of circ_DLG1 was elevated in ESCC tissues, plasma and cells. Circ_DLG1 knockdown inhibited cell cycle, proliferation, migration and invasion. MAP3K9 was highly expressed in ESCC tissues and cells, and its overexpression rescued the effects of circ_DLG1 knockdown. MiR-338-3p was a link between circ_DLG1 and MAP3K9, and circ_DLG1 regulated the expression of MAP3K9 by targeting miR-338-3p. The MAPK/ERK pathway was involved in the circ_DLG1/miR-338-3p/MAP3K9 regulatory axis. Circ_DLG1 knockdown blocked the tumor growth in vivo by regulating miR-338-3p and MAP3K9.Conclusion: Circ_DLG1 contributed to the malignant progression of ESCC by mediating the miR-338-3p/MAP3K9 axis via activating the MAPK/ERK signaling pathway. This paper provided a novel action mode of circ_DLG1 in ESCC.

scholarly journals Deoxypodophyllotoxin, a Lignan from Anthriscus sylvestris, Induces Apoptosis and Cell Cycle Arrest by Inhibiting the EGFR Signaling Pathways in Esophageal Squamous Cell Carcinoma Cells

2020 ◽  
Vol 21 (18) ◽  
pp. 6854
Author(s):  
Ah-Won Kwak ◽  
Mee-Hyun Lee ◽  
Goo Yoon ◽  
Seung-Sik Cho ◽  
Joon-Seok Choi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Reactive Oxygen Species Generation ◽  
Direct Interaction ◽  
Cyclin B1 ◽  
Dependent Manner ◽  
Anthriscus Sylvestris

Deoxypodophyllotoxin (DPT) derived from Anthriscus sylvestris (L.) Hoffm has attracted considerable interest in recent years because of its anti-inflammatory, antitumor, and antiviral activity. However, the mechanisms underlying DPT mediated antitumor activity have yet to be fully elucidated in esophageal squamous cell carcinoma (ESCC). We show here that DPT inhibited the kinase activity of epidermal growth factor receptor (EGFR) directly, as well as phosphorylation of its downstream signaling kinases, AKT, GSK-3β, and ERK. We confirmed a direct interaction between DPT and EGFR by pull-down assay using DPT-beads. DPT treatment suppressed ESCC cell viability and colony formation in a time- and dose-dependent manner, as shown by MTT analysis and soft agar assay. DPT also down-regulated cyclin B1 and cdc2 expression to induce G2/M phase arrest of the cell cycle and upregulated p21 and p27 expression. DPT treatment of ESCC cells triggered the release of cytochrome c via loss of mitochondrial membrane potential, thereby inducing apoptosis by upregulation of related proteins. In addition, treatment of KYSE 30 and KYSE 450 cells with DPT increased endoplasmic reticulum stress, reactive oxygen species generation, and multi-caspase activation. Consequently, our results suggest that DPT has the potential to become a new anticancer therapeutic by inhibiting EGFR mediated AKT/ERK signaling pathway in ESCC.

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