Antineoplastic Effects of NF-κB Inhibition by DHMEQ (Dehydroxymethylepoxyquinomicin) Alone and in Co-treatment with Radio-and Chemotherapy in Medulloblastoma Cell Lines

2018 ◽  
Vol 18 (4) ◽  
pp. 541-549 ◽  
Author(s):  
Priscila M.M. Ramos ◽  
Julia A. Pezuk ◽  
Angel M. Castro-Gamero ◽  
Harley F. Oliveira ◽  
Carlos A. Scrideli ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cell Invasion ◽  
Cell Types ◽  
Chemotherapeutic Agents ◽  
Anticancer Effect ◽  
Invasion And Migration ◽  
And Migration ◽  
Tumor Types ◽  
Medulloblastoma Cell Lines ◽  
Potential Antitumor

Background: NF-κB is a transcription factor involved in the transcriptional regulation of a large number of genes related to tumorigenesis in several cancer cell types, and its inhibition has been related to anticancer effect. DHMEQ (Dehydroxymethylepoxyquinomicin) is a compound that blocks the translocation of NF-κB from the cytoplasm to the nucleus, thus inhibiting its activity as a transcriptional activator. Several studies have shown the antineoplastic effects of DHMEQ in numerous tumor types, however, there are no surveys that tested their effects in MB. Objectives: The aim of the present study was to evaluate the effects of DHMEQ as NF-κB inhibitor in pediatric MB cell lines. Method: We used the UW402, UW473 and ONS-76 medulloblastoma (MB) cell lines to verify the effect of DHMEQ on proliferation, clonogenic capacity, apoptosis, cell invasion and migration, and evaluated the effect of the combination with other drugs and the potential as a radiosensitizator. Results: A significant decrease in the cell growth, a strong inhibition of the clonogenic capacity, migration and cell invasion was observed after NF-κB inhibition in the three MB cell lines. Conversely, increased level of apoptosis rates were demonstrated. Additionally, treatments with DHMEQ combined with other chemotherapeutic agents were synergic in most points, and a strong radiosensitization by this compound was observed in the three MB cell lines. Conclusion: DHMEQ has potential antitumor effect on MB cells, and it may be considered a new therapeutic agent to improve treatment approaches in MB.

scholarly journals Hsa_circ_0013290 Acts as Cancer-Promoting Gene in Hepatocellular Carcinoma

2021 ◽  
Vol 28 ◽  
pp. 107327482110556
Author(s):  
Xi Luo ◽  
Yicun Liu ◽  
Han Li ◽  
Tiaochun Cheng ◽  
Jianjun Wu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Lines ◽  
Cell Invasion ◽  
Cell Apoptosis ◽  
Subcellular Location ◽  
Cell Counting ◽  
Cell Cycle Distribution ◽  
Invasion And Migration ◽  
And Migration ◽  
Hcc Cells

Background As a new class of non-coding RNAs, circRNAs have been recently reported to be involved in the tumorigenesis and progression of human cancers. In the current study, we attempted to explore the potential function of a novel circRNA (hsa_circ_0013290) in hepatocellular carcinoma (HCC). Methods Relative hsa_circ_0013290 expression was analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The subcellular location of hsa_circ_0013290 was performed by RNA subcellular isolation and fluorescence in situ hybridization (FISH) assays. The effect of hsa_circ_0013290 on proliferation was detected by Cell Counting Kit-8 (CCK-8) assays. The effect of hsa_circ_0013290 on cell cycle distribution and apoptosis was detected by flow cytometry. The invasion and migration abilities of hsa_circ_0013290 were detected by transwell assays. Results Hsa_circ_0013290 is significantly upregulated in HCC cell lines and mainly located in cytoplasm of HCC cells. Hsa_circ_0013290 overexpression promotes cell invasion and migration and inhibits cell apoptosis. In contrast, hsa_circ_0013290 knockdown impedes cell invasion and migration and accelerates cell apoptosis. However, hsa_circ_0013290 did not affect cell proliferation. Conclusions Hsa_circ_0013290 is overexpressed in HCC cell lines and is mainly located in the cytoplasm of HCC cells. Hsa_circ_0013290 promotes cell invasion and migration, and inhibits cell apoptosis.

scholarly journals Characterizing the Tumor Suppressor Role of CEACAM1 in Multiple Myeloma

2018 ◽  
Vol 45 (4) ◽  
pp. 1631-1640 ◽  
Author(s):  
Jinge Xu ◽  
Bin Liu ◽  
Shoubao Ma ◽  
Jubin Zhang ◽  
Yuhan Ji ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Flow Cytometry ◽  
Tumor Suppressor ◽  
Carcinoembryonic Antigen ◽  
Cell Lines ◽  
Western Blotting ◽  
Cell Invasion ◽  
Caspase 3 ◽  
Invasion And Migration ◽  
And Migration

Background/Aims: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), also known as CD66a, is a member of the immunoglobulin (Ig) superfamily that belongs to the carcinoembryonic antigen (CEA) family which plays a dual role in cancer. Previous studies showed high expression of CEACAM1 in multiple myeloma (MM). The aim of this study was to investigate the biological consequences of CEACAM1 overexpression in MM. Methods: pEGFP-N1-CEACAM1 and pcDNA3.1-CEACAM1 expression plasmids were transfected into U-266 and RPMI8266 cell lines . Effect of CEACAM1 overexpression on the proliferation of two cell lines were tested by the CCK8 assay. Cell cycle and Apoptotic changes after CEACAM1 transfection were examined with AnnexinV–FITC/PI by flow cytometry. Hochest staining assay was used to confirm the apoptotic changes. Caspase-3 activity was examined by Western blotting. The cell invasion and migration activity change after CEACAM1 transfection were performed by well chamber assays and a wound healing, respectively. MMP-2 and MMP-9 proteins expression were detected by Western blotting. Flow cytometry immunophenotyping was be evaluated on myeloma cells from bone marrow taken from 50 patients with symptomatic MM newly diagnosed. The correlations between CEACAM1 expression levels and the clinical features across all groups were investigated. Results: CEACAM1 overexpression significantly suppressed MM cell proliferation, induced cell apoptosis, and inhibited cell invasion and migration possibly through activation of caspase-3 and downregulation of MMP-2 and MMP-9. CEACAM1 expression in patients with DS stage I was more frequent (61.5%) than those with DS stage II (21.1%) or III (22.2%). Furthermore, patients with β2-microglobulin levels equal to or less than 3.5 mg/L had higher CEACAM1 expression than those with β2-microglobulin levels greater than 3.5 mg/L. Conclusion: Our findings suggest that CEACAM1 may act as a tumor suppressor in MM.

KRAS mutation is associated with upregulation of integrin beta-4 expression leading to tumor invasion in colorectal cancer.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 576-576
Author(s):  
Seo-Hyun Choi ◽  
Michael Marco ◽  
Ching-Tung Chen ◽  
Raphael Pelossof ◽  
Kevin Patrick O'Rourke ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Tumor Microenvironment ◽  
Cell Lines ◽  
Cell Invasion ◽  
Kras Mutation ◽  
Biological Behavior ◽  
Invasion And Migration ◽  
And Migration ◽  
The Impact

576 Background: KRAS mutation ( KRASmut) is associated with aggressive biological behavior and resistance to chemoradiotherapy in colorectal cancer (CRC). The tumor microenvironment is a critical component framing the biological behavior of cancers. We have recently shown that a KRASmut modulates the tumor microenvironment by reducing the expression of extracellular matrix (ECM) genes in CRC. The effect of a KRASmut on integrins, the epithelial cell receptors for ECM proteins, remains largely unknown. Here, we investigated the impact of KRASmut on integrin expression in CRC and the effect of integrin beta 4 (ITGB4) expression on CRC phenotype. Methods: The genomic profile of 79 locally advanced rectal cancers (LARC) was characterized by the MSK-IMPACT DNA assay and RNA sequencing by Hi-Seq platform. The transcriptomic changes associated with KRAS in the LARC cohort was validated in the TCGA colon cancer dataset. Expression of ITGB4 was investigated by immunofluorescence (IF) in 39 colon cancer specimens by counting ITGB4-positive cells in an E-cadherin positive epithelial population. The relationship between KRAS and ITGB4 was also explored by manipulating KRAS expression in human cell lines and genetically engineered mouse models (GEMMs). ITGB4 knockout in HCT116 CRC cell lines and organoids from GEMMs were generated with CRISPR/Cas9. ITGB4 expression was confirmed using qRT-PCR and western blotting. Cell proliferation was assessed with the MTT assay. Cell invasion and migration were assessed in a trans-well system. Results: ITGB4 gene expression was increased in KRASmut compared to KRASwildtype in LARC and TCGA. Increased ITGB4 expression in KRASmut colon cancers was also validated by IF (p = 0.0029). Introduction of KRASmut in HCT116 CRCs and GEMMs increased ITGB4 expression by 1.5 to 2 fold. Knockout of ITGB4 reduced the migration and invasion of HCT116 CRC cells but did not alter proliferation. Conclusions: KRASmutincreases the expression of ITGB4 in CRC. Increased ITGB4 expression is associated with CRC cell invasion and migration. These results inform the biology of tumor progression in KRASmut CRC tumors.

scholarly journals MicroRNA-197 Promotes Metastasis of Hepatocellular Carcinoma by Activating Wnt/β-Catenin Signaling

2018 ◽  
Vol 51 (1) ◽  
pp. 470-486 ◽  
Author(s):  
Zhaoxia Hu ◽  
Peipei Wang ◽  
Jiaxin Lin ◽  
Xingrong Zheng ◽  
Fangji Yang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Lines ◽  
Cell Invasion ◽  
Invasion And Migration ◽  
Report System ◽  
And Migration ◽  
Signaling Activation

Background/Aims: MicroRNA-197 (miR-197) has been shown to play roles in epithelialmesenchymal transition (EMT) and metastasis. The Wnt/β-catenin pathway is associated with EMT, but whether miR-197 regulatesWnt/β-catenin remains unclear. This study was to demonstrate the role of miR-197 on the Wnt/β-catenin pathway in hepatocellular carcinoma (HCC). Methods: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-197 in 105 HCC specimens and 15 HCC cell lines. We tested the predicted target gene of miR-197 using a genetic report system. The role of miR-197 in HCC cell invasion and migration (wound healingand cell invasion and migrationby Transwell assays) and in an HCC xenograft modelwas analyzed. Results: Using a miRNA microarray analysis of HCC specimens and compared with non-metastatic HCC, miR-197 was identified as one of the most upregulated miRNAs in metastatic HCC. miR-197 expression was positively associated with the invasiveness of HCC cell lines. Metastatic HCC cells with high miR-197 expression had Wnt/β-catenin signaling activation. High levels of miR-197 expression also promoted EMT and invasionHCC cells in vitro and in vivo. miR-197 directly targeted Axin-2, Naked cuticle 1 (NKD1), and Dickkopf-related protein 2 (DKK2), leading to inhibition of Wnt/β-catenin signaling. High miR-197 expression was found in HCC specimens from patients with portal vein metastasis;high miR-197 expression correlated to the expression of Axin2, NKD1, and DKK2. Conclusion: miR-197 promotes HCC invasion and metastasis by activating Wnt/β-catenin signaling. miR-197 could possibly be used as a prognostic marker and therapeutic target for HCC.

scholarly journals Pyruvate Kinase M2 Knockdown Suppresses Migration, Invasion, and Epithelial-Mesenchymal Transition of Gastric Carcinoma via Hypoxia-Inducible Factor Alpha/B-Cell Lymphoma 6 Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Ning Li ◽  
Dandan Meng ◽  
Yue Xu ◽  
Ling Gao ◽  
Fengqian Shen ◽  
...  
Keyword(s):  
Gastric Carcinoma ◽  
Cell Lines ◽  
Cell Invasion ◽  
Epithelial Mesenchymal Transition ◽  
Hypoxia Inducible Factor ◽  
B Cell Lymphoma ◽  
Gastric Carcinoma Cell ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
And Migration

Gastric carcinoma is a common malignant cancer. Pyruvate kinase M2 (PKM2) is highly expressed in cancers, including gastric carcinoma. However, its function and molecular mechanism in gastric carcinoma remains unclear. Here, we aimed to explore the function and the underlying mechanism of PKM2 on malignant phenotypes in gastric carcinoma. In this study, the mRNA levels and protein levels of PKM2 in gastric carcinoma cell lines and normal gastric mucosa epithelial cell lines were detected using quantitative real-time PCR and western blot, respectively. PKM2 was downregulated by siRNA transfection. HIF-1α or BCL-6 was upregulated by corresponding overexpression plasmid. Cell viability was detected using CCK-8 assay. Cell invasion and migration were determined using transwell assay. Higher expression of PKM2 was observed in human gastric carcinoma cell lines MKN-45 and SGC-7901 than in the normal gastric mucosa epithelial cell line GES-1. PKM2 knockdown suppressed cancer cell invasion and migration and inhibited the epithelial-mesenchymal transition (EMT) phenotype by inhibiting E-cadherin and promoting vimentin and N-cadherin expression. Also, we observed that PKM2 knockdown suppressed the hypoxia-inducible factor alpha (HIF-1α) and B-cell lymphoma 6 (BCL-6) signaling pathway. HIF-1α overexpression reversed the function of PKM2 silencing on cell invasion, migration, EMT, and BCL-6 expression. BCL-6 overexpression also reversed the function of PKM2 silencing on cell invasion, migration, and EMT but did not affect HIF-1α expression. Taken together, data from our study suggest that PKM2 knockdown impeded cell migration, invasion, and EMT of gastric carcinoma cells via the HIF-1α/BCL-6 pathway.

Glioblastoma invasion and NMDA receptors: A novel prospect

2019 ◽  
Vol 106 (3) ◽  
pp. 250-260 ◽  
Author(s):  
DN Nandakumar ◽  
P Ramaswamy ◽  
C Prasad ◽  
D Srinivas ◽  
K Goswami
Keyword(s):  
Glutamate Receptors ◽  
Cell Lines ◽  
Intracellular Signaling ◽  
Transcript Level ◽  
Glioblastoma Cells ◽  
Invasion And Migration ◽  
Matrigel Invasion ◽  
Nmdar Activation ◽  
And Migration

Purpose Glioblastoma cells create glutamate-rich tumor microenvironment, which initiates activation of ion channels and modulates downstream intracellular signaling. N-methyl-D-aspartate receptors (NMDARs; a type of glutamate receptors) have a high affinity for glutamate. The role of NMDAR activation on invasion of glioblastoma cells and the crosstalk with α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) is yet to be explored. Main methods LN18, U251MG, and patient-derived glioblastoma cells were stimulated with NMDA to activate NMDAR glutamate receptors. The role of NMDAR activation on invasion and migration and its crosstalk with AMPAR were evaluated. Invasion and migration of glioblastoma cells were investigated by in vitro trans-well Matrigel invasion and trans-well migration assays, respectively. Expression of NMDARs and AMPARs at transcript level was evaluated by quantitative real-time polymerase chain reaction. Results We determined that NMDA stimulation leads to enhanced invasion in LN18, U251MG, and patient-derived glioblastoma cells, whereas inhibition of NMDAR using MK-801, a non-competitive antagonist of the NMDAR, significantly decreased the invasive capacity. Concordant with these findings, migration was significantly augmented by NMDAR in both cell lines. Furthermore, NMDA stimulation upregulated the expression of GluN2 and GluA1 subunits at the transcript level. Conclusions This study demonstrated the previously unexplored role of NMDAR in invasion of glioblastoma cells. Furthermore, the expression of the GluN2 subunit of NMDAR and the differential overexpression of the GluA1 subunit of AMPAR in both cell lines provide a plausible rationale of crosstalk between these calcium-permeable subunits in the glutamate-rich microenvironment of glioblastoma.

Methylation of ZNF331 Promotes Cell Invasion and Migration in Human Esophageal Cancer

2015 ◽  
Vol 16 (4) ◽  
pp. 322-328 ◽  
Author(s):  
Suzhen Jiang ◽  
Enqiang Linghu ◽  
Qimin Zhan ◽  
Weidong Han ◽  
Mingzhou Guo
Keyword(s):  
Esophageal Cancer ◽  
Cell Invasion ◽  
Invasion And Migration ◽  
And Migration ◽  
Human Esophageal Cancer

A Review on Phytopharmaceutical shaving Concomitant Experimental Anti-Diabetic and Anti-Cancer Effects as Potential Sources for Targeted Therapies Against Insulin Mediated Breast Cancer Cell Invasion and Migration

2020 ◽  
Vol 16 ◽  
Author(s):  
Vibhavana Singh ◽  
Rakesh Reddy ◽  
Antarip Sinha ◽  
Venkatesh Marturi ◽  
Shravani Sripathi Panditharadyula ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Medicinal Plants ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cell Invasion ◽  
Breast Tumor ◽  
Cancer Cell Invasion ◽  
Invasion And Migration ◽  
Anti Cancer ◽  
And Migration

: Diabetes and breast cancer are pathophysiologically similar and clinically established diseases that co-exist with a wider complex similar molecular signalling and having similar set of risk factors. Insulin plays a pivotal role for invasion and migration of breast cancer cells. Several ethnopharmacological evidences light the concomitant anti-diabetic and anti-cancer activity of medicinal plant and phytochemicals against breast tumor of patients with diabetes. This present article reviewed the findings on medicinal plants and phytochemicals with concomitant anti-diabetic and anti-cancer effects reported in scientific literature to facilitate the development of dual-acting therapies against diabetes and breast cancer. The schematic tabular form of published literatures on medicinal plants (63 plants belongs to 45 families) concluded the dynamics of phytochemicals against diabetes and breast tumor that could be explored further for the discovery of therapies for controlling of breast cancer cell invasion and migration in patient with diabetes.

scholarly journals MiR-326 mediates malignant biological behaviors of lung adenocarcinoma by targeting ZEB1

2021 ◽  
Vol 104 (2) ◽  
pp. 003685042110093
Author(s):  
Mingxin Liu ◽  
Hong Wu ◽  
Yiqiang Liu ◽  
Yan Tan ◽  
Songtao Wang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Cell Lines ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Invasion And Migration ◽  
Transwell Invasion Assay ◽  
Enhancer Binding Protein ◽  
Adenocarcinoma Cells ◽  
And Migration ◽  
Related Proteins

MiR-326 functions as an antioncogene in the several types of cancer. However, the underling mechanisms through which miRNA-326 regulates the anti-carcinogenesis of lung adenocarcinoma have remained elusive. The aim of this study was to explore the role and regulatory mechanism of miR-326 in cell proliferation, invasion, migration and apoptosis in lung adenocarcinoma. Quantitative real-time PCR (qRT-PCR) was used to detect the expression pattern of miR-326 in human bronchial epithelial cells (HBES-2B), 4 kinds of lung adenocarcinoma cell lines (H23, H1975, H2228, H2085) and 20 lung adenocarcinoma tissues. Then, H23 cells were infected with miR-326 mimics, miR-326 inhibitors and si-ZEB1 to build up-regulated miR-326 cell lines, down-regulated ZEB1(zinc-finger-enhancer binding protein 1)cell lines, simultaneous down-regulated ZEB1 and miR-326 cell lines. Moreover, CCK-8 assay, transwell invasion assay, wound healing assay and flow cytometry assay were employed to examine the effects of miR-326 and ZEB1 on the proliferation, invasion, migration and apoptosis abilities of H23 cells. Western blot was performed to explore the effects of miR-326 and ZEB1 on the expression of invasion and migration related proteins N-cadherin, E-cadherin, MMP7, MMP13, SLUG and apoptotic proteins PARP, BAX. On the mechanism, a dual-luciferase reporter gene was used to measure the target relationship between miR-326 and ZEB1. MiR-326 expression was significantly downregulated in lung adenocarcinoma tissues and cells. Overexpression of miR-326 significantly inhibited the malignant behaviors of H23 cells. Mechanically, luciferase reporter assay showed that ZEB1 was a direct target of miR-326. MiR-326 mimic downregulated the expression of ZEB1. Furthermore, knocking down ZEB1 strongly inhibited the proliferation, invasion and migration of H23 cells but promoted apoptosis. MiR-326 could target ZEB1 to inhibit the proliferation, invasion and migration of lung adenocarcinoma cells and promote apoptosis, which is a potential therapeutic target for lung adenocarcinoma.

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