scholarly journals Tissue transglutaminase-1 promotes stemness and chemoresistance in gastric cancer cells by regulating Wnt/β-catenin signaling

2016 ◽  
Vol 242 (2) ◽  
pp. 194-202 ◽  
Author(s):  
Haitao Huang ◽  
Zhiqi Chen ◽  
Xiuqin Ni
Keyword(s):  
Gastric Cancer ◽  
Wnt Signaling ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Gastric Cancer Cell ◽  
Tissue Transglutaminase ◽  
Wnt Signaling Pathway ◽  
Cancer Development ◽  
Gastric Cancer Cells ◽  
Expression Levels

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.

The Effect of Dihydroartemisinin on the Malignancy and Epithelial-Mesenchymal Transition of Gastric Cancer Cells

2019 ◽  
Vol 20 (9) ◽  
pp. 719-726 ◽  
Author(s):  
Nan Li ◽  
Suyun Zhang ◽  
Qiong Luo ◽  
Fang Yuan ◽  
Rui Feng ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Gastric Cancer Cell ◽  
Epithelial Mesenchymal Transition ◽  
Gastric Cancer Cell Line ◽  
Cancer Cell Line ◽  
Gastric Cancer Cells ◽  
Mesenchymal Transition ◽  
Expression Levels

Objective: This study aimed to observe the effects of dihydroartemisinin (DHA) on the proliferation, apoptosis, invasion, migration, and epithelial-mesenchymal transition (EMT) of the human gastric cancer cell line SGC7901 cultured in vitro. Methods: We applied varying concentrations of DHA to SGC7901 cells. Cell proliferation was measured using the cell counting kit-8 (CCK-8). Flow cytometry, Transwell invasion assay, and cell scratch assay were used to investigate the cells’ apoptosis, invasion, and migration. Western blot was used to assess the expression levels of EMT markers E-cadhein and Vimentin, protein kinases Akt and phosphorylated AKT (p-AKT), and the cell transcription factor Snail. Results: DHA can effectively inhibit the malignant proliferation of gastric cancer cells in a time- and dose-dependent manner. In this study, with longer incubation times and increased drug concentrations, the antiproliferation effect of DHA on SGC7901 cells increased gradually (P<0.05). In addition, with the increase of drug concentration, the expression levels of E-cadhein, an epithelial-mesenchymal transition marker, remarkably increased, whereas the protein expression levels of the mesenchymal markers Vimentin, Akt, p-Akt, and Snail significantly decreased (P<0.05). Conclusion: DHA can effectively inhibit the proliferation, invasion, and metastasis of the gastric cancer cell line SGC7901 and induce cancer cell apoptosis. DHA can also downregulate PI3K/AKT and Snail activities and inhibit the epithelial-mesenchymal transition of gastric cancer cells. The potential anticancer effects of DHA deserve further investigation.

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
Keyword(s):  
Gastric Cancer ◽  
Wnt Signaling ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
Gastric Epithelium ◽  
Gastric Cancer Cells ◽  
Expression Levels ◽  
Ferula Sinkiangensis ◽  
Gsk 3Β

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.

scholarly journals IFT80 Improves Invasion Ability in Gastric Cancer Cell Line via ift80/p75NGFR/MMP9 Signaling

2018 ◽  
Vol 19 (11) ◽  
pp. 3616 ◽  
Author(s):  
Rui Wang ◽  
Xiaoyan Deng ◽  
Chengfu Yuan ◽  
Hongmei Xin ◽  
Geli Liu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Reverse Transcription ◽  
Gastric Cancer Cell ◽  
Gastric Cancer Cells ◽  
Quantitative Reverse Transcription Pcr ◽  
Reverse Transcription Pcr ◽  
Gastric Cancer Cell Lines

The assembly and maintenance of cilia depend on intraflagellar transport (IFT) proteins, which play an important role in development and homeostasis. IFT80 is a newly defined IFT protein and partial mutation of IFT80 in humans causes diseases such as Jeune asphyxiating thoracic dystrophy (JATD) and short rib polydactyly (SRP) type III, both characterized by abnormal skeletal development. However, the role and mechanism of IFT80 in the invasion of gastric cancer is unknown. We established SGC-7901 and MKN-45 gastric cancer cell lines that stably overexpressed IFT80, as verified by quantitative reverse transcription-PCR, Western blot, and immunofluorescence. Matrix metalloproteinase-9 (MMP9) plays an important role in tumor invasion, and its expression was assessed by quantitative reverse transcription-PCR, Western blotting, and immunofluorescence. The invasion ability of IFT80 on SGC-7901 and MKN-45 cells was examined by the Matrigel invasion assay. The relationship between p75NGFR, and the p75NGFR antagonists, PD90780 and IFT80, were detected by quantitative reverse transcription-PCR and Western blotting. We first detected an IFT80 expression pattern, and found that IFT80 was highly expressed in gastric cancer clinical samples. Overexpression of IFT80 in the gastric cancer cell lines, SGC-7901 and MKN-45, led to lengthening cilia. Additionally, overexpression of IFT80 significantly improved proliferation and invasion, but inhibited apoptosis, in gastric cancer cells. We further found that overexpression of IFT80 increased p75NGFR and MMP9 mRNA and protein expression. Treatment with the p75NGFR antagonist PD90780 inhibited the increased invasion ability resulting from overexpression of IFT80 in SGC-7901 and MKN-45 gastric cancer cells. Thus, these results suggest that IFT80 plays an important role in invasion of gastric cancer through regulating the ift80/p75NGFR/MMP9 signal pathways.

scholarly journals GPX8 is transcriptionally regulated by FOXC1 and promotes the growth of gastric cancer cells through activating the Wnt signaling pathway

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Hong Chen ◽  
Lu Xu ◽  
Zhi-li Shan ◽  
Shu Chen ◽  
Hao Hu
Keyword(s):  
Gastric Cancer ◽  
Transcription Factor ◽  
Western Blot ◽  
Wnt Signaling ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Cancer Tissues

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.

scholarly journals Anti-Cancer Effects of Radix Angelica Sinensis (Danggui) and N-Butylidenephthalide on Gastric Cancer: Implications for REDD1 Activation and mTOR Inhibition

2018 ◽  
Vol 48 (6) ◽  
pp. 2231-2246 ◽  
Author(s):  
Kuan-Fu Liao ◽  
Tsung-Lang Chiu ◽  
Sung-Ying Huang ◽  
Teng-Fu Hsieh ◽  
Shu-Fang Chang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Survival Rate ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Gastric Cancer Cell ◽  
Angelica Sinensis ◽  
Rna Seq ◽  
Gastric Cancer Cells ◽  
Mtor Inhibition

Background/Aims: Radix Angelica Sinensis (danggui in Chinese) is widely used in traditional chinese medicine (TCM). N-butylidenephthalide (BP), a bioactive compound in danggui, is a potential antitumor agent for various cancer types. However, its clinical effect and mechanism in the treatment of gastric cancer remain undetermined. Methods: The in vivo protective effect of danggui in patients with gastric cancer were validated using data from Taiwan’s National Health Insurance Research Database (NHIRD). The genes induced by BP-treatment were analyzed by whole transcriptome RNA sequencing (RNA-seq) and validated by real-time PCR, western blot and siRNA transfection. The effect of BP on AGS cell migration and invasion was evaluated in transwell assays. The antitumor effects of BP were evaluated in vivo in an AGS xenograft animal model. Results: Danggui users were found to have an increased survival rate when compared with danggui nonusers (log-rank test p = 0.002) . The use of danggui highly associated with decreased mortality (the adjusted hazard ratio (HR) of danggui user was 0.72 [95 % CI, 0.57-0.92] (p = 0.009). The in vitro results showed that BP inhibited gastric cancer cell proliferation, and triggered cellular apoptosis depending on the activation of mitochondrial apoptotic pathway. Using RNA-seq analysis we found that REDD1 was the highest transcript induced by BP in gastric cancer cells. BP induce an increase of REDD1 expression that inhibits mTOR signaling, thus inhibiting gastric cancer growth. We used RNA interference to demonstrate that the knock-down of REDD1 attenuated the BP-induced mTORC1 activation and growth inhibition. BP suppressed the growth of AGS xenografts tumor in vivo. Conclusion: Danggui can prolong the survival rate of gastric cancer patients in Taiwan. BP caused gastric cancer cell death through the activation of mitochondria-intrinsic pathway and induced the REDD1 expression leading to mTOR signal pathway inhibition in gastric cancer cells. BP inhibited the in vivo growth of AGS xenograft tumors. These results may provide the basis for a new therapeutic approach toward the treatment of gastric cancer progression.

scholarly journals Effects of siRNA-mediated silencing of Bmi-1 gene expression on proliferation of gastric cancer cells

2019 ◽  
Vol 17 ◽  
pp. 205873921984553
Author(s):  
Ying Guo ◽  
Li Zhang ◽  
Guangyu Zhou ◽  
Qingjie Ma ◽  
Shi Gao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Flow Cytometry ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Gastric Cancer Cell ◽  
Negative Control ◽  
Control Group ◽  
Gastric Cancer Cells ◽  
Ags Cells

This study was designed to investigate the effects of siRNA-mediated silencing of Bmi-1 gene expression on proliferation of AGS gastric cancer cell. siRNA Bmi-1 was transfected into human AGS gastric cancer cells by liposome (as siRNA Bmi-1 group) with negative control (as control group); the expressions of Bmi-1 and apoptosis-related genes like P21, Bax, and Bcl-2 in AGS cells were determined by Western blot method; the apoptosis of AGS cells was detected by flow cytometry double staining and Hoechst staining; and cell cycle was measured by flow cytometry. Compared with the control group, the expression of Bmi-1 in the siRNA Bmi-1 group was significantly decreased ( P < 0.05), the apoptosis rate was increased ( P < 0.05), and cell cycles were arrested at G1 phase (P < 0.05); the expression level of P21 and Bax in cells was significantly up-regulated while that of Bcl-2 down-regulated ( P < 0.05). The down regulation of Bmi-1 can inhibit the proliferation of AGS gastric cancer cell and promote its apoptosis, which takes such effects mainly by up-regulating P21 as well as Bax and down-regulating Bcl-2.

miR-3613 Regulates Gastric Cancer Cells Proliferation, Invasion, Migration and Apoptosis by Targeting Suppressor of Cytokine Signaling 4

2019 ◽  
Vol 9 (12) ◽  
pp. 1699-1705
Author(s):  
Yuming Luo ◽  
Wei Cao
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Western Blot ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Gastric Cancer Cell ◽  
Target Genes ◽  
Luciferase Reporter ◽  
Gastric Cancer Cells ◽  
And Migration

The present study aimed to investigate the effect of miR-3613 on the biological functions of gastric cancer cell lines. The expression of miR-3613 and SOCS4 in gastric cancer cells were detected by RT-qPCR and western blot. The target genes of miR-3613 were verified with the luciferase reporter system and western blot. The SOCS4 overexpression plasmid was constructed and transfected into gastric cancer cells. To further investigate the function of miR-3613, shRNA targeting miR-3613 and SOCS4 overexpression were transfected into SGC-7901. The growth of cells was detected by CCK-8, then the cell invasion and migration ability were detected by wound healing and transwell. Furthermore, the level of cell cycle was detected by flow cytometry. The expression of cell proliferation, cyclin and migration-related proteins were detected by western blot. The results revealed that the expression of miR-3613 is significantly increased in gastric cancer cells. SOCS4 is one of the target genes of miR-3613. Additionally, interference with miR-3613 promotes cell cycle arrest in gastric cancer cells and reversed the inhibitory effect of miR-3613 on biological function of gastric cells. Collectively, the data demonstrated that miR-3613 regulates gastric cancer cell by targeting SOCS4, which is expected to be an attractive target for the development of new drugs for the treatment of gastric cancer.

scholarly journals Long Noncoding RNA KLF3-AS1 Acts as an Endogenous RNA of miR-223 to Attenuate Gastric Cancer Progression and Chemoresistance

2021 ◽  
Vol 11 ◽  
Author(s):  
Houxiang Jiang ◽  
KaiFeng Hu ◽  
Yabing Xia ◽  
Linhu Liang ◽  
Xiaoli Zhu
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Gastric Cancer Cell ◽  
Cancer Cell Proliferation ◽  
Inhibitory Effects ◽  
Gastric Cancer Cells ◽  
Gastric Cancer Cell Proliferation

Gastric cancer is a deadly disease, and the low rate of early diagnosis and chemoresistance largely contributed to the poor prognosis of gastric cancer. LncRNAs have been extensively reported for their roles in regulating cancer progression. In this study, we found that KLF3-AS1 was down-regulated in gastric cancer cells. Overexpression of KLF3-AS1 repressed gastric cancer cell proliferation, growth. In addition, KLF3-AS1 overexpression also exerted inhibitory effects on the gastric cancer cell invasion, migration and EMT, but promoted chemosensitivity of gastric cancer cells to cisplatin. The mechanistic studies showed that KLF3-AS1 could act as the “sponge” for miR-223 and to repress miR-223 expression in gastric cancer cells. Overexpression of miR-223 reversed the inhibitory effects of KLF3-AS1 overexpression on gastric cancer cell proliferation, invasion, migration and EMT, and attenuated the enhanced effects of KLF3-AS1 overexpression on gastric cancer cell chemosensitivity to cisplatin. The in vivo studies showed that KLF3-AS1 overexpression suppressed the tumor growth of SGC-7901 in the nude mice. In conclusion, our results for the first time demonstrated that KLF3-AS1 was down-regulated in gastric cancer cells and repressed gastric cancer cell proliferation, invasion, migration and EMT, and enhanced chemosensitivity to cisplatin. Further mechanistic results indicated that KLF3-AS1 exerted its biological function in gastric cancer cells by inhibiting miR-223 expression. Future studies are still required to decipher the detailed molecular mechanisms of KLF3-AS1 in gastric cancer.

scholarly journals circCOL1A1 Promotes the Progression of Gastric Cancer Cells through Sponging miR-145 to Enhance RABL3 Expression

2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Yue Ma ◽  
Yanyi Ren ◽  
Huitao Wen ◽  
Chengcheng Cui
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Gastric Cancer Cell ◽  
Circular Rna ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Gastric Cancer Cell Lines ◽  
Microrna Sponge ◽  
And Function

Circular RNA has been reported to be a new noncoding RNA which plays important roles in tumor progression. One of the most common functions of circular RNA is to regulate microRNA expression by acting as a microRNA sponge. However, the circular RNA expression profile and function remain mostly unclear in gastric cancer. In the study, we explored the expression and function of circCOL1A1 (hsa_circ_0044556) in gastric cancer. We performed RT-PCR with divergent primers, mRNA stability assay, and RNase R digestion assay to characterize circCOL1A1 in gastric cancer cell lines. qRT-PCR was applied to detect the level of circCOL1A1 in both gastric cancer cell lines and tissues. Gain- and loss-of-function studies were carried out to detect the influence of circCOL1A1 on gastric cancer cells by performing CCK8, migration, and invasion assays. The regulation of the downstream genes was identified by qRT-PCR, western blot assay, dual luciferase assay, and RNA pull-down assay. The results showed that circCOL1A1 was highly expressed in both gastric cancer cells and tissues. Silence of circCOL1A1 inhibited the proliferation, migration, and invasion of gastric cancer cells. circCOL1A1 regulated the expression of miR-145 by acting as a microRNA sponge, and the influence of circCOL1A1 could be abrogated by miR-145 mimics. Our research shows that miR-145 plays its functions through targeting and regulating RABL3. Inhibition of circCOL1A1/miR-145/RABL3 could effectively suppress gastric cancer cell proliferation, migration, and invasion. circCOL1A1 also promote the transformation of M1 into M2 macrophage. Our study identified circCOL1A1 as a novel oncogenic circRNA and will provide more information for gastric cancer therapy.

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