scholarly journals Umbelliprenin isolated from Ferula sinkiangensis inhibits tumor growth and migration through the disturbance of Wnt signaling pathway in gastric cancer

2018 ◽  
Author(s):  
Lijing Zhang ◽  
Xiaobo Sun ◽  
Jianyong Si ◽  
Guangzhi Li ◽  
Li Cao

AbstractThe traditional herb medicine Ferula sinkiangensis K. M. Shen (F. sinkiangensis) has been used to treat stomach disorders in Xinjiang District for centuries. Umbelliprenin is the effective component isolated from F. sinkiangensis which is particularly found in plants of the family Ferula. We previously reported the promising effects of Umbelliprenin against gastric cancer cells, but its anti-migration effect remained unknown. Here we investigated the anti-migration effect and mechanism of Umbelliprenin in human gastric cancer cells. In SRB assay, Umbelliprenin showed cytotoxic activities in the gastric cancer cell lines AGS and BGC-823 in a dose-and-time-dependent manner, while it showed lower cytotoxic activity in the normal gastric epithelium cell line GES-1. During transwell, scratch and colony assays, the migration of tumor cells was inhibited by Umbelliprenin treatment. The expression levels of the Wnt-associated signaling pathway proteins were analyzed with western blots, and the results showed that Umbelliprenin decreased the expression levels of proteins of the Wnt signalling pathway, such as Wnt-2, β-catenin, GSK-3β, p-GSK-3β, Survivin and c-myc. The translocation of β-catenin to the nucleus was also inhibited by Umbelliprenin treatment. In TCF reporter assay, the transcriptional activity of T-cell factor/lymphoid enhancer factor (TCF/LEF) was decreased after Umbelliprenin treatment. Thein vivo results suggested that Umbelliprenin induced little to no harm in the lung, heart and kidney. Overall, these data provided evidence that Umbelliprenin may inhibit the growth, invasion and migration of gastric cancer cells by disturbing the Wnt signaling pathway.

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Hong Chen ◽  
Lu Xu ◽  
Zhi-li Shan ◽  
Shu Chen ◽  
Hao Hu

Abstract Background Glutathione Peroxidase 8 (GPX8) as a member of the glutathione peroxidase (GPx) family plays an important role in anti-oxidation. Besides, dysregulation of GPX8 has been found in gastric cancer, but its detailed molecular mechanism in gastric cancer has not been reported. Methods Our study detected the expression of GPX8 in gastric cancer tissues and cell lines using immunohistochemistry (IHC), western blot and qRT-PCR, and determined the effect of GPX8 on gastric cancer cells using CCK-8, colony formation, transwell migration and invasion assays. Besides, the effect of GPX8 on the Wnt signaling pathway was determined by western blot. Furthermore, the transcription factor of GPX8 was identified by bioinformatics methods, dual luciferase reporter and chromatin immunoprecipitation (CHIP) assays. In addition, the effect of GPX8 on tumor formation was measured by IHC and western blot. Results The over-expression of GPX8 was observed in gastric cancer tissues and cells, which facilitated the proliferation, migration and invasion of gastric cancer cells as well as the tumor growth. GPX8 knockdown effectively inhibited the growth of gastric cancer cells and tumors. Moreover, GPX8 could activate the Wnt signaling pathway to promote the cellular proliferation, migration and invasion through. Furthermore, FOXC1 was identified as a transcription factor of GPX8 and mediated GPX8 expression to affect cell development processes. Conclusions These findings contribute to understanding the molecular mechanism of GPX8 in gastric cancer. Additionally, GPX8 can be a potential biomarker for gastric cancer therapy.


2021 ◽  
Vol 46 (2) ◽  
Author(s):  
Zhenzhen Wen ◽  
Ming Chen ◽  
Wenhao Guo ◽  
Ke Guo ◽  
Ping Du ◽  
...  

Oncology ◽  
2019 ◽  
Vol 97 (5) ◽  
pp. 311-318 ◽  
Author(s):  
Da Hyun Jung ◽  
Yoo Jin Bae ◽  
Jie-Hyun Kim ◽  
You Keun Shin ◽  
Hei-Cheul Jeung

2016 ◽  
Vol 242 (2) ◽  
pp. 194-202 ◽  
Author(s):  
Haitao Huang ◽  
Zhiqi Chen ◽  
Xiuqin Ni

Gastric cancer is a common malignancy, and is one of the most frequent causes of cancer deaths worldwide. Recently, members of the transglutaminases (TGM) family, especially TGM2, have been implicated in the progression and drug resistance of cancers, but the function of TGM1 in cancer development has been largely overlooked. In this study, we demonstrate the roles of TGM1 in development of gastric cancer. We found that expression levels of TGM1 were upregulated in both gastric cancer tissues and cultured gastric cancer cells, and that TGM1 expression levels were correlated with patient survival. In cultured gastric cancer cells, loss of TGM1 expression inhibited cell proliferation and promoted apoptosis, as well increased gastric cancer cell sensitivity to chemotherapeutic drugs and reducing stemness. These results strongly supported the participation of TGM1 in the regulation of gastric cancer development. In addition, we found evidence that the mechanism of action of TGM1 in regulating gastric cancer cell might involve the Wnt signaling pathway, as loss of TGM1 expression in gastric cancer cells led to a significant suppression of Wnt signaling activities.


2019 ◽  
Vol 156 (6) ◽  
pp. S-310-S-311
Author(s):  
Jie-Hyun Kim ◽  
Da Hyun Jung ◽  
Yoo Jin Bae ◽  
You Keun Shin ◽  
Hei Cheul Jeung

2020 ◽  
Vol 19 ◽  
pp. 153303382092807
Author(s):  
Zhenlv Lin ◽  
Fan Yang ◽  
Dong Lu ◽  
Wenjie Sun ◽  
Guangwei Zhu ◽  
...  

Objective: The aim of the study is to determine the role of nuclear receptor coactivator 2 in cell proliferation and invasion ability of gastric cancer cells and to explore its possible mechanisms. Methods: Immunohistochemical staining was used to determine NCOA2 gene expression in gastric cancer. Western blotting was used to detect Wnt signal pathways–related protein expression. Colony formation assays, Cell Counting Kit-8 assays, and transwell assays were used to determine cell proliferation, metastasis, and invasion ability of gastric cancer cells. A flow cytometric apoptosis tests determine gastric cancer cell apoptosis ability after inhibition of the expression of nuclear receptor coactivator 2. Subcutaneous mouse models were used to determine the gastric cancer growth and peritoneal metastasis differences after inhibition the expression of nuclear receptor coactivator 2. Results: The expression of nuclear receptor coactivator 2 in gastric cancer cells is high ( P < .01), including lymph node metastasis, TNM staging, and gender differences in nuclear receptor coactivator 2 expression were statistically significant ( P < .01). Short interfering nuclear receptor coactivator 2 could inhibit the proliferation and invasion ability of gastric cancer cells. Short interfering nuclear receptor coactivator 2 promotes the apoptosis of gastric cancer cells. Animal experiments showed that short interfering nuclear receptor coactivator 2 could inhibit the growth and invasion of gastric cancer-transplantable tumors. Knockdown of the expression of nuclear receptor coactivator 2 inhibited the Wnt/β-catenin signaling pathway in the gastric cancer cells. Conclusions: Knockdown of the expression of nuclear receptor coactivator 2 can inhibit the proliferation and invasion of human gastric cancer in vitro and in vivo. The underlying mechanism of NOCA2 affects the Wnt signaling pathway.


2020 ◽  
Vol 216 (7) ◽  
pp. 153001
Author(s):  
Xiumin Qi ◽  
Liang Sun ◽  
Jiayi Wan ◽  
Rongrong Xu ◽  
Songbing He ◽  
...  

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