scholarly journals Anticancer Activity of Modified Tongyou Decoction on Eca109 Esophageal Cancer Cell Invasion and Metastasis through Regulation of the Epithelial-Mesenchymal Transition Mediated by the HIF-1α-Snail Axis

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Yongsen Jia ◽  
Xin Yan ◽  
Ying Cao ◽  
Wei Song ◽  
Guangji Zhang ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Western Blot ◽  
Cell Invasion ◽  
Epithelial Mesenchymal Transition ◽  
Invasion And Metastasis ◽  
Control Groups ◽  
Transwell Assay ◽  
Scratch Assay ◽  
Mesenchymal Transition ◽  
Related Proteins

Background. To explore the activity of Modified Tongyou Decoction (MTD) against Eca109 esophageal cancer (EC) cell invasion and metastasis and to ascertain the mechanism of its anticancer activity during the epithelial-mesenchymal transition (EMT) as mediated by the HIF-1α-Snail axis. Methods. Herbal compounds were prepared by ethanol extraction, and 6 herbs composing into MTD were dipped in water-free ethanol and filtered. The filtrate was collected and centrifuged. The remains were concentrated into a paste which was adjusted to 5000mg/mL concentration with DMSO. PBS was used to dilute the herbal solution to the half maximal inhibitory concentration. A hypoxic microenvironment was induced with CoCl2 in RPMI 1640 medium, in which Eca109 cells were cultured. The cytotoxicity of MTD was determined with CCK-8 assay. The activity of MTD against cell invasion and metastasis was explored with scratch assay and transwell assay. Western blot analysis was conducted to analyze the anticancer effects of MTD on the expression of HIF-1α-Snail axis- and EMT-related proteins. Quantitative RT-PCR was used to assess the mRNA expression of Snail. Immunofluorescence labeling was performed to examine how MTD affected the coexpression of Snail and HIF-1α. Results. The fifty percent inhibitory dose of MTD was 1410 μg/mL in the normoxic environment and 1823 μg/mL in the hypoxic environment based on the CCK-8 assay. The scratch assay showed that MTD significantly inhibited cell migration in both the normoxic and hypoxic microenvironments compared with the control groups ( P  < 0.05). The transwell assay showed that MTD significantly inhibited cell invasion in both the normoxic and hypoxic environments compared with the control groups ( P  < 0.05). Western blot showed that MTD significantly inhibited the expression of the HIF-1α, Snail, Vimentin, MMP-2, MMP-9, and VE-cadherin proteins and significantly induced the expression of E-cadherin in both the normoxic and hypoxic microenvironments compared with the control groups ( P  < 0.05). qRT-PCR indicated that MTD significantly inhibited Snail mRNA expression compared with that in the control groups ( P  < 0.05). Immunofluorescence assay showed that MTD significantly inhibited the coexpression of HIF-1α and Snail in both the normoxic and hypoxic microenvironments compared with the control groups ( P  < 0.05). Conclusion. MTD downregulated HIF-1α-Snail axis- and EMT-related proteins to inhibit EC cell invasion and metastasis in both the normoxic and hypoxic environments.

FAM196B promotes proliferation and migration via regulating epithelial-mesenchymal transition in esophageal cancer

2021 ◽  
pp. 1-8
Author(s):  
Haifeng Xia ◽  
Fang Hu ◽  
Liangbin Pan ◽  
Chengcheng Xu ◽  
Haitao Huang ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Western Blot ◽  
Cox Regression ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Cox Regression Analysis ◽  
Ec Cells ◽  
And Migration ◽  
Proliferation And Migration

BACKGROUND: EC (esophageal cancer) is a common cancer among people in the world. The molecular mechanism of FAM196B (family with sequence similarity 196 member B) in EC is still unclear. This article aimed to clarify the role of FAM196B in EC. METHODS: The expression of FAM196B in EC tissues was detected using qRT-PCR. The prognosis of FAM196B in EC patients was determined by log-rank kaplan-Meier survival analysis and Cox regression analysis. Furthermore, shRNA was used to knockdown the expression of FAM196B in EC cell lines. MTT, wound healing assays and western blot were used to determine the role of FAM196B in EC cells. RESULTS: In our research, we found that the expression of FAM196B was up-regulated in EC tissues. The increased expression of FAM196B was significantly correlated with differentiation, lymph node metastasis, stage, and poor survival. The proliferation and migration of EC cells were inhibited after FAM196B-shRNA transfection in vitro and vivo. The western blot result showed that FAM196B could regulate EMT. CONCLUSION: These results suggested that FAM196B severs as an oncogene and promotes cell proliferation and migration in EC. In addition, FAM196B may be a potential therapeutic target for EC patients.

scholarly journals Knockdown of ARK5 Expression Suppresses Invasion and Metastasis of Gastric Cancer

2017 ◽  
Vol 42 (3) ◽  
pp. 1025-1036 ◽  
Author(s):  
Dehu Chen ◽  
Guiyuan Liu ◽  
Ning Xu ◽  
Xiaolan You ◽  
Haihua Zhou ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Western Blot ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Invasion And Metastasis ◽  
Ags Cells ◽  
Mesenchymal Transition

Background/Aims: Gastric cancer (GC) is a common and lethal malignancy, and AMP-activated protein kinase-related kinase 5 (ARK5) has been discovered to promote cancer metastasis in certain types of cancer. In this study, we explored the role of ARK5 in GC invasion and metastasis. Methods: ARK5 and epithelial-mesenchymal transition (EMT)-related markers were determined by immunohistochemistry and western blot in GC specimens. Other methods including stably transfected against ARK5 into SGC7901 and AGS cells, western blot, migration and invasion assays in vitro and nude mice tumorigenicity in vivo were also employed. Results: The results demonstrated that ARK5 expression was increased and positively correlated with metastasis, EMT-related markers and poor prognosis in patients with GC. Knockdown of ARK5 expression remarkably suppressed GC cells invasion and metastasis via regulating EMT, rather than proliferation in vitro and in vivo. And knockdown of ARK5 expression in GC cells resulted in the down-regulation of the mTOR/p70S6k signals, Slug and SIP1. Conclusion: The elevated ARK5 expression was closely associated with cancer metastasis and patient survival, and it seemed to function in GC cells migration and invasion via EMT alteration, together with the alteration of the mTOR/p70S6k signals, Slug and SIP1, thus providing a potential therapeutic target for GC.

scholarly journals MicroRNA-200b suppresses cell invasion and metastasis by inhibiting the epithelial-mesenchymal transition in cervical carcinoma

2016 ◽  
Vol 13 (4) ◽  
pp. 3155-3160 ◽  
Author(s):  
YAN-XIANG CHENG ◽  
QI-FAN ZHANG ◽  
LI HONG ◽  
FENG PAN ◽  
JIN-LING HUANG ◽  
...  
Keyword(s):  
Cervical Carcinoma ◽  
Cell Invasion ◽  
Epithelial Mesenchymal Transition ◽  
Invasion And Metastasis ◽  
Mesenchymal Transition

scholarly journals TRPP2 Enhances Metastasis by Regulating Epithelial-Mesenchymal Transition in Laryngeal Squamous Cell Carcinoma

2016 ◽  
Vol 39 (6) ◽  
pp. 2203-2215 ◽  
Author(s):  
Kaile Wu ◽  
Bing Shen ◽  
Feifei Jiang ◽  
Lin Xia ◽  
Taotao Fan ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Wound Healing ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cell Invasion ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Invasion And Metastasis ◽  
Mesenchymal Transition ◽  
Expression Levels

Background/Aim: Surgery and chemotherapy treatments of human laryngeal squamous cell carcinoma (HLSCC) may fail due to metastasis, in which epithelial-mesenchymal transition (EMT) plays an important role. TRPP2, a nonselective cation channel, is expressed in various cell types and participates in many biological processes. Here, we show that TRPP2 enhanced metastasis by regulating EMT. Methods: We used immunohistochemistry, western blotting, Ca2+ imaging, transwell and wound healing assays to investigate TRPP2 expression levels in HLSCC tissue, and the role of TRPP2 in invasion and metastasis of a human laryngocarcinoma cell line (Hep2 cell). Results: We found that TRPP2 protein expression levels were significantly increased in HLSCC tissue; higher TRPP2 levels were associated with decreased patient survival time and degree of differentiation and advanced clinical stage. Knockdown of TRPP2 by transfection with TRPP2 siRNA markedly suppressed ATP-induced Ca2+ release, wound healing, and cell invasion in Hep2 cells. Moreover, TRPP2 siRNA significantly decreased vimentin expression but increased E-cadherin expression in Hep2 cells. In the EMT signalling pathway, TRPP2 siRNA significantly decreased Smad4, STAT3, SNAIL, SLUG and TWIST expression in Hep2 cells. Conclusion: We revealed a previously unknown function of TRPP2 in cancer development and a TRPP2-dependent mechanism underlying laryngocarcinoma cell invasion and metastasis. Our results suggest that TRPP2 may be used as a biomarker for evaluating patient prognosis and as a novel therapeutic target in HLSCC.

scholarly journals Transketolase Serves a Poor Prognosticator in Esophageal Cancer by Promoting Cell Invasion via Epithelial-Mesenchymal Transition

2016 ◽  
Vol 7 (13) ◽  
pp. 1804-1811 ◽  
Author(s):  
Yin-Kai Chao ◽  
Ta-Lun Peng ◽  
Wen-Yu Chuang ◽  
Chi-Ju Yeh ◽  
Yan-Liang Li ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Cell Invasion ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition

scholarly journals Galectin-1 From Cancer-Associated Fibroblasts Promotes the Invasion and Metastasis of Gastric Cancer Through TGF-β1-Induced Epithelial-Mesenchymal Transition

2021 ◽  
Author(s):  
xiaolan you ◽  
Jian Wu ◽  
Xiaojun Zhao ◽  
Xingyu Jiang ◽  
Wenxuan Tao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Invasion ◽  
Epithelial Mesenchymal Transition ◽  
Cancer Associated Fibroblasts ◽  
Invasion And Metastasis ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
And Migration ◽  
Tgf Β1

Abstract Background The gastric cancer (GC) microenvironment has important effects on biological behaviors, such as tumor cell invasion and metastasis. However, the mechanism by which the GC microenvironment promotes GC cell invasion and metastasis is unknown. The present study aimed to clarify the effects and mechanism of galectin-1 (GAL-1, encoded by LGALS1) on GC invasion and metastasis in the GC microenvironment.Methods The expression of GAL-1/ LGALS1 was determined using western blotting, immunohistochemistry, and quantitative real-time reverse transcription PCR in GC tissues. Besides, methods including stable transfection, Matrigel invasion and migration assays, and wound-healing assays in vitro; and metastasis assays in vivo, were also conducted.Results GAL-1 from cancer-associated fibroblasts (CAFs) induced the epithelial‑mesenchymal transition (EMT) of GC cells though the transforming growth factor beta (TGF-β1)/ Sma- and mad-related protein (Smad) pathway, and affected the prognosis of patients with GC. The level of GAL-1 was high in CAFs, and treating MGC-803 and SGC -7901 cell line with the conditioned medium from CAFs promoted their invasion and metastasis abilities. Overexpression of LGALS1 promoted the expression of TGF-β1 and induced EMT of GC cell lines. A TGF-β1 antagonist inhibited the invasion and migration of GC cells. In vivo, overexpression of LGALS1 promoted GC growth and metastasis, and the TGF-β1 antagonist dramatically reversed these events. Conclusions These findings suggested that high expression of GAL-1 in the GC microenvironment predicts a poor prognosis in patients with GC by promoting the migration and invasion of GC cells via EMT through the TGF-β1/Smad signaling pathway. The results might provide new therapeutic targets to treat GC.

scholarly journals The Inflammatory Profile of the Tumor Microenvironment, Orchestrated by Cyclooxygenase-2, Promotes Epithelial-Mesenchymal Transition

2021 ◽  
Vol 11 ◽  
Author(s):  
Fernán Gómez-Valenzuela ◽  
Enrico Escobar ◽  
Ricardo Pérez-Tomás ◽  
Viviana P. Montecinos
Keyword(s):  
Tumor Microenvironment ◽  
Cell Invasion ◽  
Epithelial Mesenchymal Transition ◽  
Review Article ◽  
Cyclooxygenase 2 ◽  
Invasion And Metastasis ◽  
Mesenchymal Transition ◽  
Previous Evidence ◽  
Cox 2 ◽  
Inflammatory Profile

The tumor microenvironment (TME) corresponds to a complex and dynamic interconnection between the extracellular matrix and malignant cells and their surrounding stroma composed of immune and mesenchymal cells. The TME has constant cellular communication through cytokines that sustain an inflammatory profile, which favors tumor progression, angiogenesis, cell invasion, and metastasis. Although the epithelial-mesenchymal transition (EMT) represents a relevant metastasis-initiating event that promotes an invasive phenotype in malignant epithelial cells, its relationship with the inflammatory profile of the TME is poorly understood. Previous evidence strongly suggests that cyclooxygenase-2 (COX-2) overexpression, a pro-inflammatory enzyme related to chronic unresolved inflammation, is associated with common EMT-signaling pathways. This review article summarizes how COX-2 overexpression, within the context of the TME, orchestrates the EMT process and promotes initial metastatic-related events.

scholarly journals Periostin Mediates TGF-β-Induced Epithelial Mesenchymal Transition in Prostate Cancer Cells

2015 ◽  
Vol 36 (2) ◽  
pp. 799-809 ◽  
Author(s):  
Qingfeng Hu ◽  
Shijun Tong ◽  
Xiaojun Zhao ◽  
Weihong Ding ◽  
Yuancheng Gou ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Western Blot ◽  
Cancer Cells ◽  
Cell Invasion ◽  
Associated Factors ◽  
Epithelial Mesenchymal Transition ◽  
Prostate Cancer Cells ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
And Migration

Background: In our previous study, we found that periostin was upregulated in prostate cancer, and its expression could be modulated by TGF-β. TGF-β could upregulate periostin expression in some cells, and both TGF-β and periostin could induce epithelial mesenchymal transition (EMT). We aimed to study the effect of periostin in the process of TGF-β-induced EMT in prostate cancer cells. Methods: We constructed a lentivirus vector containing the periostin gene and transduced it into PC3 and DU145 cells. After confirming periostin overexpression by PCR and Western blotting, we used an MTT assay to establish a growth curve to measure cell proliferation. Additionally, we performed transwell and wound healing assays to measure cell invasion and migration, respectively. Lastly, we measured the expression of EMT associated factors using Western blot analysis to test the effect of periostin on EMT in prostate cancer cells. Results: PCR and Western blot analyses confirmed that periostin was upregulated after infection with the periostin lentiviral vector. Periostin overexpression promoted increased cell proliferation, invasion, and migration as measured by MTT, transwell, and wound healing assays, respectively. Western blot analysis illustrated that periostin overexpression increased the expression of EMT associated factors, and periostin overexpression activated Akt and GSK-3β, which could be inhibited using a PI3K inhibitor. Additionally, TGF-β increased the levels of STAT3, Twist1 and periostin, while both STAT3 shRNA and Twist1 shRNA inhibited periostin expression. However, STAT3 shRNA also decreased Twist1 expression. Although reduction of STAT3, Twist1 or periostin levels with shRNA inhibited TGF-β-induced overexpression of EMT associated factors, periostin overexpression could reverse such inhibition by interfering with STAT3 and Twist1. Similarly, periostin overexpression also reversed inhibition of cell invasion induced by interference of STAT3 and Twist1. Conclusion: Our findings indicate that periostin is an important mediator of TGF-β-induced EMT and suggest that periostin is a potential therapeutic target for suppressing the metastatic progression of prostate cancer.

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