WIN 55,212-2 Inhibits the Epithelial Mesenchymal Transition of Gastric Cancer Cells via COX-2 Signals

Xian, Xiang-Shu; Huang, Lanqing; Zhang, Bo; Wu, Chi‐Rei; Cui, Jun; Wang, Zhihua

doi:10.1159/000447910

Cited by 25 publications

(14 citation statements)

References 32 publications

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“…The metastasis of epithelial tumors involves a series of phenotypic changes, known as the EMT. Cannabinoids have been reported to inhibit EMT in gastric, endometrial and NSCLC cancer cells [4,34,51]. However, this important property of cannabinoids has not been extensively investigated.…”

Section: Discussionmentioning

confidence: 99%

“…Finally, A549, H460 and H1792 cells were exposed to 20 ng/ml EGF in order to analyze cell migration, as previously reported [34]. As summarized in Fig 5, EGF induces cell migration in the three types of cancer cell used.…”

Section: Cannabinoids Inhibit Egf-induced Cell Motility In Cancer Cellsmentioning

confidence: 93%

“…The wound healing assay was performed as previously described [34]. A549, H460 and H1792 cells were cultured to confluence in six-well culture plates.…”

Section: Wound Healing Assaymentioning

confidence: 99%

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Cannabinoid receptor expression in non-small cell lung cancer. Effectiveness of tetrahydrocannabinol and cannabidiol inhibiting cell proliferation and epithelial-mesenchymal transition in vitro

Milián

Mata

Alcácer³

et al. 2020

PLoS ONE

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Background/ObjectivePatients with non-small cell lung cancer (NSCLC) develop resistance to antitumor agents by mechanisms that involve the epithelial-to-mesenchymal transition (EMT). This necessitates the development of new complementary drugs, e.g., cannabinoid receptors (CB1 and CB2) agonists including tetrahydrocannabinol (THC) and cannabidiol (CBD). The combined use of THC and CBD confers greater benefits, as CBD enhances the effects of THC and reduces its psychotropic activity. We assessed the relationship between the expression levels of CB1 and CB2 to the clinical features of a cohort of patients with NSCLC, and the effect of THC and CBD (individually and in combination) on proliferation, EMT and migration in vitro in A549, H460 and H1792 lung cancer cell lines. MethodsExpression levels of CB1, CB2, EGFR, CDH1, CDH2 and VIM were evaluated by quantitative reverse transcription-polymerase chain reaction. THC and CBD (10-100 μM), individually or in combination (1:1 ratio), were used for in vitro assays. Cell proliferation was determined by BrdU incorporation assay. Morphological changes in the cells were visualized by phase-contrast and fluorescence microscopy. Migration was studied by scratch recolonization induced by 20 ng/ml epidermal growth factor (EGF).

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Section: Discussionmentioning

confidence: 99%

Section: Cannabinoids Inhibit Egf-induced Cell Motility In Cancer Cellsmentioning

confidence: 93%

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Cannabinoid receptor expression in non-small cell lung cancer. Effectiveness of tetrahydrocannabinol and cannabidiol inhibiting cell proliferation and epithelial-mesenchymal transition in vitro

Milián

Mata

Alcácer³

et al. 2020

PLoS ONE

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“…Various drugs have been intensively researched in many animal experiments and clinical trials for gastric cancer [33, 34]. Some studies have indicated that chemopreventive compounds in dietary foods are a potential source of safe bioactive compounds for cancer chemoprevention and suppression of proliferation via the primary target of ROS that damages DNA and the activation of signaling pathways, as well as the expression of proteins involved in the induction of apoptosis [12, 13, 19].…”

Section: Discussionmentioning

confidence: 99%

A Comparative Proteomic Analysis of Erinacine A’s Inhibition of Gastric Cancer Cell Viability and Invasiveness

Kuo

Lee

et al. 2017

Cell Physiol Biochem

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Background / Aims: Erinacine A, isolated from the ethanol extract of the Hericium erinaceus mycelium, has been demonstrated as a new alternative anticancer medicine. Drawing upon current research, this study presents an investigation of the molecular mechanism of erinacine A inhibition associated with gastric cancer cell growth. Methods: Cell viability was determined by Annexin V–FITC/propidium iodide staining and migration using a Boyden chamber assay to determine the effects of erinacine A treatment on the proliferation capacity and invasiveness of gastric cancer cells. A proteomic assay provided information that was used to identify the differentially-expressed proteins following erinacine A treatment, as well as the mechanism of its targets in the apoptotic induction of erinacine A. Results: Our results demonstrate that erinacine A treatment of TSGH 9201 cells increased cytotoxicity and the generation of reactive oxygen species (ROS), as well as decreased the invasiveness. Treatment of TSGH 9201 cells with erinacine A resulted in the activation of caspases and the expression of TRAIL. Erinacine A induction of apoptosis was accompanied by sustained phosphorylation of FAK/AKT/p70S6K and the PAK1 pathways, as well as the generation of ROS. Furthermore, the induction of apoptosis and anti-invasion properties by erinacine A could involve the differential expression of the 14-3-3 sigma protein (1433S) and microtubule-associated tumor suppressor candidate 2 (MTUS2), with the activation of the FAK/AKT/p70S6K and PAK1 signaling pathways. Conclusions: These results lead us to speculate that erinacine A may generate an apoptotic cascade in TSGH 9201 cells by activating the FAK/AKT/p70S6K/PAK1 pathway and upregulating proteins 1433S and MTUS2, providing a new mechanism underlying the anti-cancer effects of erinacine A in human gastric cancer cells.

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“…COX-2 has been reported to be a mediator of TGF-β1-induced EMT (24). However, whether it plays a key role in EMT induced by TGF-β1 in TCC has not been clarified.…”

Section: Cox-2 Upregulation Is Essential For Tgf-β1-induced Emtmentioning

confidence: 99%

Silibinin attenuates TGF‑β1‑induced migration and invasion via EMT suppression and is associated with COX‑2 downregulation in bladder transitional cell carcinoma

Sun

Jia

et al. 2018

Oncol Rep

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Transforming growth factor (TGF)-β1 is highly expressed in bladder transitional cell carcinoma (TCC) and is positively associated with tumor grade. TGF-β1 signaling promotes cell metastasis by inducing epithelial-mesenchymal transition (EMT), however, the underlying mechanisms are not fully understood. Our previous study demonstrated the anti-metastatic effects of silibinin, a natural flavonoid derived from milk thistle, against TCC. The present study investigated the effects of silibinin on TGF-β1-induced EMT in TCC, focusing on the role of prostaglandin-endoperoxide synthase 2 (COX-2). Cell migration was determined by a wound healing assay and Transwell migration assay, and cell invasion was investigated using a Transwell invasion assay. Cell morphology was observed using an inverted microscope. Cell viability was evaluated by an MTT and cell counting assays. EMT markers were detected by reverse transcription-quantitative polymerase chain reaction and western blotting. Specific small interfering RNA was used to knockdown COX-2 gene expression. TGF-β1 promoted cell migration and invasion, induced EMT and upregulated the expression of COX-2. COX-2 knockdown attenuated TGF-β1-induced EMT, indicating that COX-2 upregulation was essential for TGF-β1-induced EMT. Silibinin attenuated TGF-β1-induced migration and invasion by inhibiting EMT, and was associated with COX-2 downregulation. TGF-β1-induced COX-2 upregulation, which was inhibited by silibinin. In addition, TGF-β1-induced EMT was further inhibited when silibinin treatment was combined with COX-2-knockdown. The results suggested that silibinin may be a potential future treatment for metastatic TCC.

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WIN 55,212-2 Inhibits the Epithelial Mesenchymal Transition of Gastric Cancer Cells via COX-2 Signals

Cited by 25 publications

References 32 publications

Cannabinoid receptor expression in non-small cell lung cancer. Effectiveness of tetrahydrocannabinol and cannabidiol inhibiting cell proliferation and epithelial-mesenchymal transition in vitro

Cannabinoid receptor expression in non-small cell lung cancer. Effectiveness of tetrahydrocannabinol and cannabidiol inhibiting cell proliferation and epithelial-mesenchymal transition in vitro

A Comparative Proteomic Analysis of Erinacine A’s Inhibition of Gastric Cancer Cell Viability and Invasiveness

Silibinin attenuates TGF‑β1‑induced migration and invasion via EMT suppression and is associated with COX‑2 downregulation in bladder transitional cell carcinoma

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