Antimetastatic Effects of <i>Celastrus orbiculatus</i> on Human Gastric Adenocarcinoma by Inhibiting Epithelial–Mesenchymal Transition and NF-κB/Snail Signaling Pathway

Zhu, Yuqing; Liu, Yanqing; Qian, Yayun; Dai, Xiaojun; Yang, Lin; Chen, Jue; Guo, Shiyu; Hisamitsu, Tadashi

doi:10.1177/1534735415572880

Cited by 32 publications

(35 citation statements)

References 30 publications

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“…External stimuli can separate these factors from IkB, transfer them to the nucleus, and allow them to interact with their target genes to promote cancer cell motility and invasion. Inhibition of the EMT and NF-kB/Snail signaling pathway has been shown to significantly suppress metastasis in multiple cancer cell types, such as gastric adenocarcinoma cells SGC-7901 (Zhu et al, 2015) and breast cancer cells A2780 (Liu et al, 2015a). Moreover, suppression of the NF-kB activity and EMT-related proteins, such as vimentin, Snail, and Slug, has been shown to suppress metastasis in osteosarcoma cell lines MG-63, Saos-2, and U-2OS (Chang et al, 2015), indicating that cancer metastasis can be effectively suppressed by inhibiting the EMT and NF-kB/Snail signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Tim-3 facilitates osteosarcoma proliferation and metastasis through the NF-κB pathway and epithelial-mesenchymal transition

Feng¹,

Guo²

2016

Genet. Mol. Res.

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ABSTRACT. The aim of this study was to investigate the expression of T-cell immunoglobulin mucin domain molecule-3 (Tim-3) in osteosarcoma tissues, and analyze its effect on cell proliferation and metastasis in an osteosarcoma cell line. Tim-3 mRNA and protein expression in osteosarcoma tissue was detected by reverse transcriptase-polymerase chain reaction and immunohistochemistry, respectively. Additionally, the cell viability, apoptosis rate, and invasive ability of the osteosarcoma cell line MG-63 were tested using the methyl thiazolyl tetrazolium assay, Annexin V-propidium iodide flow cytometry, and a Transwell assay, respectively, following Tim-3 interference using small interfering RNA (siRNA). We also analyzed the expression of Snail, E-cadherin, vimentin, and nuclear factor (NF)-kB in the cells by western blot. We observed that Tim-3 mRNA and protein was significantly overexpressed in osteosarcoma tissues, compared to the adjacent normal tissue (P < 0.01). Moreover, MG-63 cells transfected with the Tim-3 siRNA presented lower cell viability, a greater number of apoptotic cells, and decreased invasive ability (P < 0.01), compared to control cells. Additionally, we observed a decrease in Snail and vimentin expression, an increase in the E-cadherin level, and an increase in NF-kB p65 phosphorylation (P < 0.01) in Tim-3 siRNA-transfected MG-63 cells. Based on these results, we concluded that Tim-3 is highly expressed in osteosarcoma tissue. Moreover, we speculated that interfering in Tim-3 expression could significantly suppress osteosarcoma cell (MG-63) proliferation and metastasis via the NF-kB/Snail signaling pathway and epithelial-mesenchymal transition.

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Section: Discussionmentioning

confidence: 99%

Tim-3 facilitates osteosarcoma proliferation and metastasis through the NF-κB pathway and epithelial-mesenchymal transition

Feng¹,

Guo²

2016

Genet. Mol. Res.

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“…Currently, it is generally accepted that the suppression of E-cadherin expression mainly occurs at transcriptional level, and several transcription factors that repress its transcription have been recognized, including zinc finger factors snail, slug, zeb1 and zeb2, basic helixloop-helix factors E47 and twist [27][28][29]. Furthermore, increasing evidence revealed that these transcription factors could be regulated via several signaling cascades, including ERK pathway, Akt pathway and NF-κB pathway [30][31][32].…”

Section: Introductionmentioning

confidence: 99%

Knockdown of Radixin Suppresses Gastric Cancer Metastasis In Vitro by Up-Regulation of E-Cadherin via NF-κB/Snail Pathway

Zhu

Yan

et al. 2016

Cell Physiol Biochem

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Background/Aims: Radixin has recently been shown to correlate with the metastasis of gastric cancer, but the pathogenesis is elusive. Adhesion proteins contribute to the regulation of metastasis, and thus this study sought to investigate the role of radixin in the migration, invasion and adhesion of gastric cancer cells, as well as its interaction with adhesion proteins in vitro. Methods: Radixin stable knockdown human gastric carcinoma SGC-7901 cells were constructed. Alterations in the migration, invasion and adhesion ability were examined by matrigel-coated plate and transwell assays. The expression pattern of adhesion proteins, including E-cadherin, β-catenin and claudin-1, was determined by quantitative real-time PCR and western blot. Possible involvement of NF-κB/snail pathway was also evaluated. Results: Stable knockdown of radixin significantly suppressed migration and invasion, but enhanced adhesion in SGC-7901 cells. The expression of E-cadherin was manifestly increased in radixin knockdown cells, whereas the expression of β-catenin and claudin-1 was unchanged. The nuclear exclusion of NF-κB followed by conspicuous reduction of snail expression was involved in the regulation of E-cadherin expression. Conclusions: Radixin knockdown suppresses the metastasis of SGC-7901 cells in vitro by up-regulation of E-cadherin. The NF-κB/snail pathway contributes to the regulation of E-cadherin in response to depletion of radixin.

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“…In addition, it has been revealed that COE is able to inhibit tumor metastasis in gastric cancer (8). The results of these studies suggested that COE may also have the ability to inhibit the invasion and metastasis of NPC cells, the validation of which was an aim of the present study.…”

Section: Introductionmentioning

confidence: 80%

“…Although a number of studies have suggested that the COE is associated with tumor metastasis (8,14), its function in the EZH2/ROCK1 signaling pathway remains unclear. To identify potential therapeutic targets, elucidating the underlying molecular tumorigenic mechanisms of COE is required.…”

Section: Discussionmentioning

confidence: 99%

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Efficacy of extracts of Celastrusï¿½orbiculatus in suppressing migration and invasion by inhibiting the EZH2/ROCK1 signaling pathway in human nasopharyngeal carcinoma

et al. 2018

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Abstract. Celastrus orbiculatus extract (COE) has been used in folk medicine in China for the treatment of a number of diseases. In the laboratory, COE exhibits a variety of anticancer functions, including inhibition of metastasis. However, the underlying molecular anti-metastatic mechanism in nasopharyngeal carcinoma (NPC) cells remains unclear. The aim of the present study was to determine whether the anti-metastatic effect of COE was involved in inhibiting migration and invasion of human NPC cells. In vitro, cell viability and apoptosis of 5-8F cells were analyzed using an MTS assay and flow cytometry, respectively. Invasion and migration of 5-8F cells were analyzed using a Transwell assay. Protein and mRNA expression levels of 5-8F cells were analyzed by western blot analysis and the reverse transcription-quantitative polymerase chain reaction, respectively. COE significantly decreased cell viability in 5-8F cells and inhibited enhancer of zeste homolog 2 (EZH2) and Rho-associated coiled coil-containing protein kinase 1 (ROCK1) expression at the mRNA and protein levels. Furthermore, COE decreased the migration and invasion of 5-8F cells in a dose-dependent manner. The results of the present study suggested that COE prevents migration and invasion by suppressing the EZH2/ROCK1 signaling pathway in NPC cells. On the basis of the results of the present study, COE may be a novel anticancer agent for the treatment of metastasis in NPC.

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Antimetastatic Effects of Celastrus orbiculatus on Human Gastric Adenocarcinoma by Inhibiting Epithelial–Mesenchymal Transition and NF-κB/Snail Signaling Pathway

Cited by 32 publications

References 30 publications

Tim-3 facilitates osteosarcoma proliferation and metastasis through the NF-κB pathway and epithelial-mesenchymal transition

Tim-3 facilitates osteosarcoma proliferation and metastasis through the NF-κB pathway and epithelial-mesenchymal transition

Knockdown of Radixin Suppresses Gastric Cancer Metastasis In Vitro by Up-Regulation of E-Cadherin via NF-κB/Snail Pathway

Efficacy of extracts of Celastrusï¿½orbiculatus in suppressing migration and invasion by inhibiting the EZH2/ROCK1 signaling pathway in human nasopharyngeal carcinoma

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