Selective COX-2 Blockade Inhibits Lung Adenocarcinoma Cell Migration in vitro

Background and objective: Proviral insertion site in Moloney murine leukemia virus (PIM)2 functions as a serine/threonine kinase to participate in regulating cell proliferation and cell cycle. PIM2 has been shown to be elevated in the lung cancer cell lines. This study was performed to investigate the role of PIM2 in lung adenocarcinoma cell growth. Mateial and methods: Expression level of PIM2 in lung adenocarcinoma tissues and cells was detected by qRT-PCR (quantitative Reverse Transcription PCR) and western blot. The over-expression and knockdown of PIM2 were separately established by employing pcDNA and siRNA to explore the effects on the cell viability, apoptosis, invasion and migration. The downstream pathways were evaluated by western blot assay. Results: Lung adenocarcinoma tissues and cells showed an elevation of both PIM2 mRNA and protein expression. Knocking down PIM2 decreased the cell viability and promoted the apoptosis, which can be reversed by pcDNA-mediated over-expression of PIM2. PIM2 silencing suppressed the promotional effect of over-expression of PIM2 on cell invasion and migration through increasing IκBα expression and decreasing the X-linked inhibitor of apoptosis protein (XIAP), p65 and IκBα phosphorylation. While, over-expression of PIM2 showed opposite effect on IκBα and XIAP expression or p65 and IκBα phosphorylation. Conclusion: PIM2 can not only suppress lung adenocarcinoma cell apoptosis but also promote cell migration and invasion depending on XIAP/NF-κB signaling pathway.

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Lung Adenocarcinoma Cell Responses in a 3D in Vitro Tumor Angiogenesis Model Correlate with Metastatic Capacity

ACS Biomaterials Science & Engineering ◽

10.1021/acsbiomaterials.7b00011 ◽

2017 ◽

Vol 4 (2) ◽

pp. 368-377 ◽

Cited By ~ 6

Author(s):

Laila C. Roudsari ◽

Sydney E. Jeffs ◽

Jennifer L. West

Keyword(s):

Lung Adenocarcinoma ◽

Tumor Angiogenesis ◽

Adenocarcinoma Cell ◽

Cell Responses ◽

Metastatic Capacity ◽

Angiogenesis Model

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Compound Injection of Shenqi as a Reversal Drug on Docetaxel Resistant Human Lung Adenocarcinoma Cell A549/DTX

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.926-930.1054 ◽

2014 ◽

Vol 926-930 ◽

pp. 1054-1057

Author(s):

Xiao Dong Liu ◽

Yi Ju Hou ◽

Lin Zhang ◽

Hui Ling Cao

Keyword(s):

Drug Resistance ◽

Lung Adenocarcinoma ◽

Human Lung ◽

Adenocarcinoma Cell ◽

Human Lung Adenocarcinoma ◽

Docetaxel Resistance ◽

Mtt Method ◽

Reversal Index ◽

Human Lung Adenocarcinoma Cell

To investigate the effect and the mechanism of compound injection of Shenqi (Codonopsis and Astragalus) on Docetaxel resistance of human lung adenocarcinoma cell A549/ DTX. The cytotoxicities of Shenqi Injection were assayed with the MTT method, the effects of Shenqi Injection on apoptosis induced by Docetaxel in A549/ DTX was examined by flow cytometry (FCM). The expression levels of apoptosis regulator Bc1-2 and Bax were detected by Western blot. After treatment with Shenqi Injection for 24 hours, results showed that 15 μL / mL Shenqi Injection significantly increased toxicity of Docetaxel on A549/DTX. Shenqi Injection could reverse the Docetaxel resistance in A549/ DTX in vitro. The drug resistance reversal index (RI) was equal to 2.71 analyzed with MTT method. Shenqi Injection could enhance the apoptosis effect of Docetaxel on A549/DTX. We conclude that Shenqi Injection can reverse the drug resistance on A549/DTX, and its mechanism is to promote apoptosis may be related with the up-regulation of Bc1-2 expression and down-regulation of Bax expression.

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Ursodeoxycholic acid protects against intestinal barrier breakdown by promoting enterocyte migration via EGFR- and COX-2-dependent mechanisms

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00354.2017 ◽

2018 ◽

Vol 315 (2) ◽

pp. G259-G271 ◽

Cited By ~ 15

Author(s):

Jamie M. Golden ◽

Oswaldo H. Escobar ◽

Michelle V. L. Nguyen ◽

Michael U. Mallicote ◽

Patil Kavarian ◽

...

Keyword(s):

Cell Migration ◽

Epithelial Cell ◽

Ursodeoxycholic Acid ◽

Intestinal Epithelial Cell ◽

Growth Factor Receptor ◽

Intestinal Barrier ◽

Intestinal Epithelial ◽

Epithelial Cell Migration ◽

Cox 2

The intestinal barrier is often disrupted in disease states, and intestinal barrier failure leads to sepsis. Ursodeoxycholic acid (UDCA) is a bile acid that may protect the intestinal barrier. We hypothesized that UDCA would protect the intestinal epithelium in injury models. To test this hypothesis, we utilized an in vitro wound-healing assay and a mouse model of intestinal barrier injury. We found that UDCA stimulates intestinal epithelial cell migration in vitro, and this migration was blocked by inhibition of cyclooxygenase 2 (COX-2), epidermal growth factor receptor (EGFR), or ERK. Furthermore, UDCA stimulated both COX-2 induction and EGFR phosphorylation. In vivo UDCA protected the intestinal barrier from LPS-induced injury as measured by FITC dextran leakage into the serum. Using 5-bromo-2′-deoxyuridine and 5-ethynyl-2′-deoxyuridine injections, we found that UDCA stimulated intestinal epithelial cell migration in these animals. These effects were blocked with either administration of Rofecoxib, a COX-2 inhibitor, or in EGFR-dominant negative Velvet mice, wherein UDCA had no effect on LPS-induced injury. Finally, we found increased COX-2 and phosphorylated ERK levels in LPS animals also treated with UDCA. Taken together, these data suggest that UDCA can stimulate intestinal epithelial cell migration and protect against acute intestinal injury via an EGFR- and COX-2-dependent mechanism. UDCA may be an effective treatment to prevent the early onset of gut-origin sepsis. NEW & NOTEWORTHY In this study, we show that the secondary bile acid ursodeoxycholic acid stimulates intestinal epithelial cell migration after cellular injury and also protects the intestinal barrier in an acute rodent injury model, neither of which has been previously reported. These effects are dependent on epidermal growth factor receptor activation and downstream cyclooxygenase 2 upregulation in the small intestine. This provides a potential treatment for acute, gut-origin sepsis as seen in diseases such as necrotizing enterocolitis.

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CRMP2 as a Candidate Target to Interfere with Lung Cancer Cell Migration

Biomolecules ◽

10.3390/biom11101533 ◽

2021 ◽

Vol 11 (10) ◽

pp. 1533

Author(s):

Xabier Morales ◽

Rafael Peláez ◽

Saray Garasa ◽

Carlos Ortiz de Solórzano ◽

Ana Rouzaut

Keyword(s):

Cell Migration ◽

Lung Adenocarcinoma ◽

Cancer Cell ◽

Adaptor Protein ◽

Mechanistic Explanation ◽

In Vitro Assays ◽

Cancer Cell Migration ◽

Cortical Actin

Collapsin response mediator protein 2 (CRMP2) is an adaptor protein that adds tubulin dimers to the growing tip of a microtubule. First described in neurons, it is now considered a ubiquitous protein that intervenes in processes such as cytoskeletal remodeling, synaptic connection and trafficking of voltage channels. Mounting evidence supports that CRMP2 plays an essential role in neuropathology and, more recently, in cancer. We have previously described a positive correlation between nuclear phosphorylation of CRMP2 and poor prognosis in lung adenocarcinoma patients. In this work, we studied whether this cytoskeleton molding protein is involved in cancer cell migration. To this aim, we evaluated CRMP2 phosphorylation and localization in the extending lamella of lung adenocarcinoma migrating cells using in vitro assays and in vivo confocal microscopy. We demonstrated that constitutive phosphorylation of CRMP2 impaired lamella formation, cell adhesion and oriented migration. In search of a mechanistic explanation of this phenomenon, we discovered that CRMP2 Ser522 phospho-mimetic mutants display unstable tubulin polymers, unable to bind EB1 plus-Tip protein and the cortical actin adaptor IQGAP1. In addition, integrin recycling is defective and invasive structures are less evident in these mutants. Significantly, mouse xenograft tumors of NSCLC expressing CRMP2 phosphorylation mimetic mutants grew significantly less than wild-type tumors. Given the recent development of small molecule inhibitors of CRMP2 phosphorylation to treat neurodegenerative diseases, our results open the door for their use in cancer treatment.

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