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1.
Chin J Physiol ; 62(5): 210-216, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31670285

RESUMO

Matrix metalloproteinases-2 (MMP2) has been reported to be overexpressed in various types of cancer. However, the contribution of various genotypes of MMP2 to lung cancer is controversial and not yet been examined in Taiwan. Therefore, in the current study, we investigated the association of MMP2 genotypes with lung cancer risk among Taiwanese. In this hospital-based, case-control study, 358 lung cancer patients and 716 age- and gender-matched healthy controls were recruited, and the genotypic distributions of MMP2-1306 and MMP2- 735 were determined. Then, their association with lung cancer was evaluated, and their interaction with personal smoking status was also examined via stratification analysis. The results showed that the percentages of variant CT and TT at MMP2-1306 were 17.3% and 1.7% among the lung cancer patients, respectively, much lower than those of 28.7% and 2.4%, respectively, among the healthy controls (P for trend = 0.0001). The allelic frequency distribution analysis showed that the variant T allele at MMP2-1306 conferred a statistically significantly lower lung cancer risk than the wild-type C allele (adjusted odds ratio = 0.54, 95% confidence interval = 0.41-0.72, P = 0.0001). There was an obvious effect of MMP2-1306 genotype on lung cancer risk among the subpopulations of ever smokers but not nonsmokers. As for the genotypes of MMP2-735, there was no such differential distribution in the aspects of genotypic or allelic frequencies, or combinative effects with smoking status. The genotypes of MMP2-1306 may act as a biomarker in determining personal susceptibility to lung cancer in Taiwan. The contribution of MMP2 genotypes alone and its joint effects with personal cigarette smoking habit on lung cancer susceptibility should be taken into consideration of the clinical practices for early detection and prediction of lung cancer in Taiwan.


Assuntos
Predisposição Genética para Doença , Neoplasias Pulmonares , Metaloproteinase 2 da Matriz/genética , Estudos de Casos e Controles , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Taiwan
2.
Anticancer Res ; 39(8): 4485-4490, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366549

RESUMO

BACKGROUND/AIM: Intraductal papillary mucinous neoplasm (IPMN) has a variety of histological and morphological appearances. Matrix metalloproteinases (MMPs) have been considered to be associated with tumor progression or poor prognosis. The aim of this study was to elucidate the molecular basis of IPMN variation in different types of lesions. MATERIALS AND METHODS: The expression of MMP-1,2,7,9 in 51 cases of IPMN were investigated. The MMP score was calculated as the sum of the score of staining distribution and the score of the intensity staining. RESULTS: MMP scores were correlated with histological grade, histological subtype, and type of invasion. MMP high expression groups (MMP score ≥5) had worse prognosis than low-expression groups. CONCLUSION: MMP expression varied between different types of IPMN, a result supporting differences in molecular basis of malignancies. These considerations may be helpful for optimal management or treatment according to various types of IPMN.


Assuntos
Metaloproteinase 1 da Matriz/genética , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 7 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Neoplasias Intraductais Pancreáticas/genética , Idoso , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Pessoa de Meia-Idade , Pâncreas/metabolismo , Pâncreas/patologia , Neoplasias Intraductais Pancreáticas/epidemiologia , Neoplasias Intraductais Pancreáticas/patologia
3.
J Agric Food Chem ; 67(32): 8855-8867, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31343893

RESUMO

Abalone (Haliotis discus hannai) is a precious seafood in the market. It has been reported that biological active substances derived from abalone have anti-oxidative, anti-inflammatory, anti-bacterial, and anti-thrombosis potential. However, there were few studies to assess whether they have anti-cancer potential. In this study, we evaluated the anti-metastasis and anti-pro-angiogenic factors and mechanism of action of boiled abalone byproduct peptide (BABP, EMDEAQDPSEW) in human fibrosarcoma (HT1080) cells and human umbilical vein endothelial cells (HUVECs). The results demonstrated that BABP treatment significantly lowers migration and the invasion of HT1080 cells and HUVECs. BABP inhibits phorbol 12-myristate 13-acetate (PMA)-induced matrix metalloproteinase (MMP) expression and activity by blocking mitogen-activated protein kinases (MAPKs) and NF-κB signaling and hypoxia-induced vascular endothelial growth factor (VEGF) secretion and hypoxia inducible factor (HIF)-1α accumulation through suppressing the AKT/mTOR signal pathway. BABP treatment inhibits VEGF-induced VEGFR-2 expression and tube formation in HUVECs. The effect of BABP on anti-metastatic and anti-vascular activity in HT1080 cells and HUVECs revealed that BABP may be a potential pharmacophore for tumor therapy in the future.


Assuntos
Inibidores da Angiogênese/farmacologia , Antineoplásicos/farmacologia , Gastrópodes/química , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Peptídeos/farmacologia , Resíduos/análise , Inibidores da Angiogênese/química , Inibidores da Angiogênese/isolamento & purificação , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Metástase Neoplásica , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Neovascularização Patológica/fisiopatologia , Peptídeos/química , Peptídeos/isolamento & purificação , Frutos do Mar/análise , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
4.
Medicine (Baltimore) ; 98(24): e15831, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31192912

RESUMO

BACKGROUND: Severe acute pancreatitis (SAP) is a severe form of inflammatory disease with a high mortality rate. Ulinastatin, as a urinary trypsin inhibitor (UTI), is a glycoprotein playing a critical role in SAP. Consequently, we identified the hypothesis that both matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) gene polymorphisms might promote the efficacy of ulinastatin in SAP. METHODS: A total of 235 patients with SAP were treated by intravenous drip of ulinastatin for the duration of 10 days. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed for testing the distribution of genotypes and alleles frequency of MMP-2 and MMP-9 gene polymorphisms, and analyzing association of MMP-2 rs243865, MMP-2 rs2285053, MMP-9 rs3918242, or MMP-9 rs17576 with efficacy of ulinastatin in patients with SAP. Shesis software was adopted for analyzing single genotypes of MMP-2 and MMP-9 gene polymorphisms site A Generalized Multifactor Dimensionality Reduction (GMDR) model and a logistic regression analysis were used for analyzing effect of MMP-2 and MMP-9 gene polymorphisms on the efficacy of ulinastatin in treating patients with SAP. RESULTS: CC genotype of MMP-2 gene rs243865 C>T was observed to have a better positive effect in promoting the efficacy of ulinastatin in comparison with CT and TT genotypes. Haplotype CCTG, CCTA, CTTG, and CTTA were combined by MMP-2 and MMP-9 gene polymorphisms which have the ability to increase the efficacy of ulinastatin in treating patients with SAP. MMP-2 gene rs243865 C>T site polymorphism was served as a favorable factor while the MMP-9 gene rs3918242 C>T site polymorphism was noticed as an unfavorable factor for the efficacy of ulinastatin in treating patients with SAP. CONCLUSION: The key findings clearly demonstrated that both the MMP-2 rs243865 and MMP-9 rs3918242 gene polymorphisms served as biological indicators for the efficacy of ulinastatin in treating patients with SAP.


Assuntos
Glicoproteínas/administração & dosagem , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Pancreatite/tratamento farmacológico , Variantes Farmacogenômicos , Inibidores da Tripsina/administração & dosagem , Adulto , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genótipo , Glicoproteínas/uso terapêutico , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Resultado do Tratamento , Inibidores da Tripsina/uso terapêutico
5.
J Toxicol Sci ; 44(6): 425-433, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31168029

RESUMO

Cardiac fibroblasts (CFs) could be activated after myocardial infarction (MI). Thus, it is necessary to explore effective drugs to suppress the activation of CFs following MI. This study was designed to investigate the impacts of ellagic acid on CFs and the underlying mechanisms. The expression of histone deacetylases (HDACs) and fibrosis-related genes was detected by qRT-PCR and western blot. The Masson's Trichrome Staining assay was used to evaluate the area of cardiac fibrosis. The proliferation and migration of CFs were measured by CCK8 Kit and Transwell assay, respectively. Our results showed that ellagic acid significantly reduced protein expression of HDAC1, mRNA expression of collagen I, collagen III, MMP-2 and MMP-9 and the area of cardiac fibrosis in MI rats. In Ang II-stimulated CFs, ellagic acid (60 µmol/L) decreased the protein expression of HDAC1, collagen I, collagen III, MMP-2 and MMP-9, and inhibited cell proliferation and migration. Further, HDAC1 over-expression reversed the inhibitor effects of ellagic acid on proteins expression (collagen I, collagen III, MMP-2 and MMP-9) and proliferation and migration of CFs. The present results suggested that ellagic acid suppressed proliferation and migration of CFs by down-regulating expression of HDAC1.


Assuntos
Cardiotônicos/farmacologia , Ácido Elágico/farmacologia , Fibroblastos/efeitos dos fármacos , Angiotensina II , Animais , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Colágeno Tipo I/genética , Colágeno Tipo III/genética , Regulação para Baixo , Fibroblastos/fisiologia , Regulação da Expressão Gênica/efeitos dos fármacos , Histona Desacetilase 1/genética , Masculino , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Miocárdio/citologia , Ratos Sprague-Dawley
6.
Chem Biol Interact ; 309: 108716, 2019 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-31207222

RESUMO

BACKGROUND: Neferine (NEF) is a major bisbenzylisoquinline alkaloid mainly exists in the seed embryo of Nelumbo nucifera (Gaertn.) that possesses anti-tumor effects. Our study designed to check the effect of NEF on breast cancer MDA-MB-231 cells and further explore the potential mechanism. METHODS: MDA-MB-231 cells were administrated with various dosages of NEF for 24 h after which cell viability was measured. The effects of NEF on cell proliferation, apoptosis, migration and invasion were assessed by BrdU staining, flow cytometry assay and Transwell assay. Western blot was utilized to assess the accumulation of proteins related with proliferation, apoptosis, metastasis, PI3K/AKT and MEK/ERK pathways. RESULTS: Viability was efficiently reduced by NEF in a dose-dependent manner. NEF (8 µM) significantly suppressed cell proliferation, migration and invasion but enhanced apoptosis in MDA-MB-213 cells. Interestingly, NEF suppressed miR-374a expression and miR-374a mediated the inhibitory effect of NEF. Moreover, miR-374a positively regulated FGFR-2 expression and FGFR-2 overexpression impeded the effect of NEF on MDA-MB-213 cells. FGFR-2 overexpression abolished the suppressive effect of NEF on PI3K/AKT and MEK/ERK pathways. CONCLUSION: We found that NEF possessed the anti-growth and anti-metastasis effect on MDA-MB-231 cells through regulating miR-374a/FGFR-2, which might provide new insight for breast cancer management.


Assuntos
Benzilisoquinolinas/farmacologia , Proliferação de Células/efeitos dos fármacos , MicroRNAs/metabolismo , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismo , Antagomirs/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Feminino , Humanos , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/antagonistas & inibidores , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Transdução de Sinais/efeitos dos fármacos
7.
Cell Mol Biol Lett ; 24: 39, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31205475

RESUMO

Background: The aim of this study was to investigate the effect of human umbilical vein endothelial cells on epithelial-to-mesenchymal transition of the cervical cancer cell line SiHa by studying the Notch1/lysyl oxidase (LOX)/SNAIL1 pathway. Methods: Monocultures of SiHa cells, SiHa cells containing a control sequence, and Notch1-silenced SiHa cells, as well as co-cultures of human umbilical vein endothelial cells with SiHa cells and Notch1-silenced SiHa cells, were established. The invasiveness of SiHa cells in each group was evaluated using a Transwell assay. The mRNA levels of E-cadherin and vimentin were detected using quantitative real-time polymerase chain reaction. The expression levels of the matrix metalloproteinases MMP-2 and MMP-9 were determined in SiHa cells using an immunofluorescence assay and the protein activity was detected by gelatin zymography. Changes in LOX, SNAIL1 and NOTCH1 expression in the SiHa cells in each group were detected using western blotting. Results: Compared with monocultured SiHa cells, co-cultured SiHa cells showed a significant increase in their invasiveness and expression levels of vimentin, as well as of NOTCH 1, LOX, and SNAIL1, whereas their expression of E-cadherin was significantly reduced and protein activities of MMP-2 and MMP-9 were increased. Compared with SiHa, mono- and co-cultured NOTCH 1-silenced SiHa cells showed significant reductions in their invasiveness and expression levels of vimentin, NOTCH 1, LOX, and SNAIL1, whereas their expression of E-cadherin significantly increased and protein activities of MMP-2 and MMP-9 decreased. Conclusion: Co-culture with human umbilical vein endothelial cells promoted the epithelial-to-mesenchymal transition of SiHa cells by activating the NOTCH1/LOX/SNAIL1 pathway in SiHa cells, which enhanced their invasive and metastatic capacities. The results of this study may provide a new perspective on cervical cancer metastasis and a theoretical basis for clinical treatment.


Assuntos
Técnicas de Cocultura/métodos , Transição Epitelial-Mesenquimal , Proteína-Lisina 6-Oxidase/metabolismo , Receptor Notch1/metabolismo , Transdução de Sinais , Fatores de Transcrição da Família Snail/metabolismo , Neoplasias do Colo do Útero/metabolismo , Linhagem Celular Tumoral , Células Endoteliais , Feminino , Regulação da Expressão Gênica , Células Endoteliais da Veia Umbilical Humana , Humanos , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Neoplasias do Colo do Útero/fisiopatologia
8.
Environ Toxicol ; 34(10): 1085-1093, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31184425

RESUMO

Geraniin has been reported to have numerous biological activities, including antiviral, antihypertensive, antihyperglycaemic, liver protective, antidiabetic, and apoptotic activities. However, the anti-migration effects of geraniin on oral cancer remain elusive. In this study, we revealed the potential antitumor mechanisms of geraniin through the inhibition of the migration and invasion of human oral cancer cell lines SCC-9 and SCC-14. The results of gelatin zymography and Western blot assays revealed that geraniin significantly reduced the activity and expression of matrix metalloproteinase-2 (MMP-2) of oral cancer cells in a concentration-dependent manner. Furthermore, geraniin potently suppressed the phosphorylation of focal adhesion kinase (FAK), Src, and extracellular signal-regulated kinase (ERK)1/2 but did not affect the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase 1/2. Moreover, blocking the MAPK/ERK1/2 pathway significantly enhanced the anti-migration ability of geraniin in oral cancer cells. In conclusion, we demonstrated that geraniin inhibits the motility of SCC-9 and SCC-14 cells in vitro through a molecular mechanism that involves the attenuation of MMP-2 expression and activity mediated by decreased FAK/Src and ERK1/2 pathways.


Assuntos
Antineoplásicos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Glucosídeos/farmacologia , Taninos Hidrolisáveis/farmacologia , Metaloproteinase 2 da Matriz/metabolismo , Neoplasias Bucais/metabolismo , Quinases da Família src/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proteína-Tirosina Quinases de Adesão Focal/genética , Geranium/química , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Metaloproteinase 2 da Matriz/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Neoplasias Bucais/genética , Neoplasias Bucais/fisiopatologia , Quinases da Família src/genética
9.
Anticancer Res ; 39(5): 2429-2435, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31092435

RESUMO

BACKGROUND/AIM: Perfluorooctanoic acid (PFOA) is one of the most common perfluorinated compounds widely used in several applications. Due to its persistence in the environment, PFOA has been associated with various diseases, including cancer. This study explored the effects of PFOA on follicular thyroid carcinoma cells (FTC133). MATERIALS AND METHODS: Cell invasion, migration, adhesion and activity of matrix metalloproteinase-2 (MMP-2) were investigated using Transwell assays, adhesion assay and gelatin zymography, respectively. The underlying mechanism involved in the effects observed was evaluated by immunoblot analyses. RESULTS: Treatment with PFOA did not affect cell migration, but enhanced cell invasion, adhesion and activity of MMP-2 in FTC133 cells. PFOA selectively enhanced the phosphorylation of nuclear factor kappa B (NF-κB) p65, as well as induced NF-κB nuclear translocation. Treatment with a NF-κB inhibitor (BAY 11-7085) was able to reverse PFOA-induced cell invasiveness. CONCLUSION: PFOA promotes invasiveness of FTC133 cells mediated through the activation of NF-κB signaling.


Assuntos
Adenocarcinoma Folicular/tratamento farmacológico , Caprilatos/farmacologia , Fluorcarbonetos/farmacologia , Metaloproteinase 2 da Matriz/genética , Fator de Transcrição RelA/genética , Adenocarcinoma Folicular/genética , Adenocarcinoma Folicular/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , NF-kappa B/antagonistas & inibidores , NF-kappa B/genética , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Nitrilos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Sulfonas/farmacologia , Fator de Transcrição RelA/antagonistas & inibidores , Ativação Transcricional/efeitos dos fármacos
10.
Biomed Res Int ; 2019: 5318729, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31119174

RESUMO

The high invasion and metastasizing abilities of hepatocellular carcinoma (HCC) are the primary reasons for the high mortality rate of patients. Therefore, identification of agents to inhibit invasion and metastasis is very important for treatment of HCC. We analyzed the anti-invasion and antimetastatic effects of porcine recombinant NK-lysin, which was designed and expressed in vitro by our research group, on SMMC-7721 hepatocellular carcinoma cells via wound-healing assays, adhesion assays, invasion assays, real-time polymerase chain reaction (PCR), and Western blot analysis. MTT assay results indicated that NK-lysin inhibited the growth of SMMC-7721 cells in a dose- and time-dependent manner. NK-lysin reduced the ability of cell migration, adhesion, and invasion. Based on gene and protein expression analysis, NK-lysin decreased ß-catenin and MMP-2 expression. These results suggested that NK-lysin has anti-invasion and antimetastatic effects on hepatocellular carcinoma cells in vitro by reducing the level of the ß-catenin and MMP-2.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Metaloproteinase 2 da Matriz/genética , Proteolipídeos/farmacologia , beta Catenina/genética , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Metaloproteinase 9 da Matriz/genética , Invasividade Neoplásica/patologia , Invasividade Neoplásica/prevenção & controle , Metástase Neoplásica , Suínos
11.
Mol Med Rep ; 19(6): 4935-4945, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31059086

RESUMO

Previous reports have indicated a potential link between microRNA (miR)­214 and hypoxia. In the present study, the biological functions and potential mechanisms of miR­214 were determined, as well as its correlation with HIF­1α signaling in non­small cell lung cancer (NSCLC) cells. Quantitative polymerase chain reaction revealed that miR­214 expression was upregulated in lung cancer tissues compared with adjacent normal tissues. miR­214 mimics were transfected into A549 cells, and MTT, colony formation, invasion and wound healing assays were performed. It was demonstrated that miR­214 mimic transfection promoted the invasion, proliferation and migration of A549 cells. Furthermore, miR­214 inhibitor transfection decreased H1299 cell invasion, proliferation and migration. Next, the association between miR­214 expression and the HIF­1α signaling cascade was examined. It was demonstrated that miR­214 mimics upregulated the expression of hypoxia­inducible factor (HIF)­1α, vascular endothelial growth factor (VEGF), adenylate kinase 3 and matrix metalloproteinase (MMP)2, whereas miR­214 inhibitor downregulated the expression of these factors. Using prediction software, it was demonstrated that tumor suppressor ING4 was a target of miR­214. A luciferase reporter assay confirmed that ING4 was a direct target of miR­214. There was a negative correlation between ING4 and miR­214 expression in lung cancer tissues. In addition, ING4 siRNA and plasmid was transfected into cells in order to validate its effect on HIF­1α, MMP2 and VEGF expression. ING4 overexpression downregulated HIF­1α and its targets MMP2 and VEGF, while ING4 siRNA upregulated HIF­1α, MMP2 and VEGF. In conclusion, it was demonstrated that miR­214 targeted ING4 in lung cancer cells, and upregulated the HIF­1α cascade, leading to MMP2 and VEGF upregulation. This approach may help to clarify the role of miRNA in non­small lung cancer and may be a new therapeutic target for non­small lung cancer.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Proteínas de Homeodomínio/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Pulmonares/patologia , MicroRNAs/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Células A549 , Adenilato Quinase/genética , Adenilato Quinase/metabolismo , Adulto , Idoso , Antagomirs/metabolismo , Proteínas de Ciclo Celular/antagonistas & inibidores , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Proteínas de Homeodomínio/antagonistas & inibidores , Proteínas de Homeodomínio/genética , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Neoplasias Pulmonares/metabolismo , Masculino , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Pessoa de Meia-Idade , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Proteínas Supressoras de Tumor/antagonistas & inibidores , Proteínas Supressoras de Tumor/genética , Fator A de Crescimento do Endotélio Vascular/genética
12.
Mol Carcinog ; 58(8): 1492-1501, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31087358

RESUMO

Cellular nucleic acid-binding protein (CNBP) is associated with cell proliferation, and its expression is elevated in human tumors, but the molecular mechanisms of CNBP in tumor cell biology have not been fully elucidated. In this study, we report that CNBP is a transcription factor essential for regulating matrix metalloproteinases mmp-2, mmp-14, and transcription factor e2f2 gene expression by binding to their promoter regions via a sequence-specific manner. Importantly, epidermal growth factor stimulation is required to induce CNBP phosphorylation and nuclear transport, thereby promoting the expression of mmp-2, mmp-14, and e2f2 genes. As a consequence, loss of cnbp attenuates the ability of tumor cell growth, invasion, and migration. Conversely, overexpression of cnbp is associated with tumor cell biology. Collectively, our findings reveal CNBP as a key transcriptional regulator of tumor-promoting target genes to control tumor cell biology.


Assuntos
Fator de Transcrição E2F2/biossíntese , Metaloproteinase 14 da Matriz/biossíntese , Metaloproteinase 2 da Matriz/biossíntese , Neoplasias/patologia , Proteínas de Ligação a RNA/metabolismo , Transporte Ativo do Núcleo Celular/fisiologia , Animais , Linhagem Celular , Proliferação de Células , Fator de Transcrição E2F2/genética , Células HEK293 , Humanos , Metaloproteinase 14 da Matriz/genética , Metaloproteinase 2 da Matriz/genética , Camundongos , Neoplasias/genética , Fosforilação , Regiões Promotoras Genéticas/genética , Ligação Proteica , RNA Mensageiro/biossíntese , Proteínas de Ligação a RNA/genética , Transcrição Genética/genética , Regulação para Cima/genética
13.
Artif Cells Nanomed Biotechnol ; 47(1): 2091-2097, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31131637

RESUMO

In previous studies, numerous dysregulated lncRNAs were identified using RNA-sequencing. Lung cancer is the most common malignant tumour worldwide and the second leading cause in cancer. The aim of this study is to investigate the function and mechanism of lincRNA00858 in the lung cancer. RT-PCR was used to detect the expression of lincRNA00858. Proliferation, invasion, and epithelial-mesenchymal transition (EMT) were examined by CCK8, transwell assay and western blot to evaluate the function of linc00858. Dual-luciferase reporter assay was used to identified the potential target of linc00858. Over-expression of linc00858 significantly promoted cell proliferation, invasion. We also found that linc00858 facilitated the EMT process. Dual-luciferase reporter assay revealed that linc00858 can bind with miR-3182 directly. Linc00858 can negatively regulate the expression of miR-3182. Further experiments demonstrated that MMP2 was the direct target of miR-3182. Rescue experiments revealed that linc00858 functioned through miR-3182/MMP2 axis. Taken together, we verified the role of an unknown linc00858 in lung cancer and provided its mechanism. Mechanistically, linc00858 acted as a competitive endogenous RNA to sponged miR-3182 and regulate MMP2 in lung cancer. Our study provided new clues for understanding the mechanism of lung cancer.


Assuntos
Progressão da Doença , Neoplasias Pulmonares/patologia , Metaloproteinase 2 da Matriz/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Sequência de Bases , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Humanos
14.
Int J Mol Sci ; 20(9)2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31035654

RESUMO

Several clinical studies have suggested the impact of sinusoidal and pulsed electromagnetic fields in quickening wound repair processes and tissue regeneration. The clinical use of extremely low-frequency electromagnetic fields could represent a novel frontier in tissue repair and oral health, with an interesting clinical perspective. The present study aimed to evaluate the effect of an extremely low-frequency sinusoidal electromagnetic field (SEMF) and an extremely low-frequency pulsed electromagnetic field (PEMF) with flux densities of 1 mT on a model of oral healing process using gingival fibroblasts. An in vitro mechanical injury was produced to evaluate wound healing, migration, viability, metabolism, and the expression of selected cytokines and protease genes in fibroblasts exposed to or not exposed to the SEMF and the PEMF. Interleukin 6 (IL-6), transforming growth factor beta 1 (TGF-ß), metalloproteinase 2 (MMP-2), monocyte chemoattractant protein 1 (MCP-1), inducible nitric oxide synthase (iNOS), and heme oxygenase 1 (HO-1) are involved in wound healing and tissue regeneration, favoring fibroblast proliferation, chemotaxis, and activation. Our results show that the exposure to each type of electromagnetic field increases the early expression of IL-6, TGF-ß, and iNOS, driving a shift from an inflammatory to a proliferative phase of wound repair. Additionally, a later induction of MMP-2, MCP-1, and HO-1 was observed after electromagnetic field exposure, which quickened the wound-healing process. Moreover, electromagnetic field exposure influenced the proliferation, migration, and metabolism of human gingival fibroblasts compared to sham-exposed cells. This study suggests that exposure to SEMF and PEMF could be an interesting new non-invasive treatment option for wound healing. However, additional studies are needed to elucidate the best exposure conditions to provide the desired in vivo treatment efficacy.


Assuntos
Campos Eletromagnéticos , Fibroblastos/metabolismo , Fibroblastos/efeitos da radiação , Gengiva/citologia , Biomarcadores , Proliferação de Células , Citocinas , Expressão Gênica , Humanos , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Cicatrização/efeitos da radiação
15.
J BUON ; 24(2): 853-858, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31128046

RESUMO

PURPOSE: Plant metabolites have gained considerable attention as the anticancer agents over the last few decades. Previous studies have indicated the potential of taxifolin as an anticancer agent. However, the information on the anticancer activity of taxifolin against skin scar cell carcinoma as well as several other types of cancers is scantly. Against this background, the present study was designed to investigate the anticancer activity of taxifolin against a panel of skin scar cell carcinoma cell lines. MATERIALS AND METHODS: Proliferation rate of the cells was monitored by MTT assay. DAPI and annexin V/PI assay was used to investigate the induction of apoptosis. Flow cytometery was employed to carry out the cell cycle analysis. Transwell assay was used to check the invasion of the cancerous cells. RESULTS: The results indicated that taxifolin inhibits the growth of the skin scar cell carcinoma cell lines. However the anticancer effects were more profound on the SSCC cancer cells (IC50, 20 µM). In contrast the anticancer effects of taxifolin on the non-cancerous skin cells were minimal. Further investigation revealed that the anticancer effects of taxifolin on the SSCC cells is due to the induction of apoptosis and cell cycle arrest. Moreover, taxifolin could also inhibit the invasion of SSCC cells which was associated with downregulation of the MMP-2 and MMP-9 expression indicative of the potential of taxifolin in the treatment of scar cell carcinoma Conclusion: It is was found that taxifolin inhibited the growth of skin scar cell carcinoma growth by triggering apoptosis and cell cycle arrest and also inhibited cell invasion capacity and therefore this study warrants further investigation on the anticancerous potential of taxifolin.


Assuntos
Carcinoma/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Quercetina/análogos & derivados , Neoplasias Cutâneas/tratamento farmacológico , Apoptose/efeitos dos fármacos , Carcinoma/genética , Carcinoma/patologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Cicatriz/patologia , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Quercetina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Serina-Treonina Quinases TOR/genética
16.
Cell Physiol Biochem ; 52(6): 1255-1266, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31026389

RESUMO

BACKGROUND/AIMS: Praeruptorins, a seselin-type coumarin, possess anti-inflammatory and antitumor promoting properties. However, molecular mechanisms through which Praeruptorin-B (Pra-B) exerts an antimetastatic effect on cervical cancer cells remain unclear. METHODS: Cell viability was examined using the MTT assay, whereas cell migration and invasion were examined using the Boyden chamber assay. Western blotting and RT-PCR were performed to investigate the inhibitory effect of Pra-B on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced matrix metalloproteinase-2/-9 (MMP-2/-9) expression in HeLa cells. The findings of the luciferase assay confirmed the inhibitory effect of Pra-B on TPA-induced transcriptional activity of MMP2/-9 in HeLa cells. RESULTS: Pra-B inhibited TPA-induced metastatic ability of human cervical cancer cells without any significant toxicity. Pra-B suppressed TPA-induced mRNA and protein expression and transcriptional activity of MMP-2/-9 in HeLa cells. Furthermore, Pra-B inhibited AKT phosphorylation but did not affect the MAPK pathway. Cotreatment of HeLa cells with TPA plus Pra-B or LY294002 (a PI3K inhibitor) reduced cell invasion and MMP-2/-9 expression and transcriptional activity. In addition, Pra-B attenuated TPA-induced nuclear translocation of NF-κB-p65/-p50, which reduced Ikk-α phosphorylation in HeLa cells. Cotreatment of HeLa cells with TPA plus Pra-B or LY294002 reduced NF-κB nuclear translocation. CONCLUSION: These results suggested that Pra-B-mediated inhibition of TPA-induced cell metastasis involved the suppression of p-AKT/NF-κB via MMP-2/-9 expression in HeLa cells. Pra-B can be a potential antimetastatic agent against cervical cancer.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Cumarínicos/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Invasividade Neoplásica/prevenção & controle , Transdução de Sinais/efeitos dos fármacos , Neoplasias do Colo do Útero/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Células HeLa , Humanos , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , NF-kappa B/metabolismo , Invasividade Neoplásica/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Acetato de Tetradecanoilforbol , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo
17.
Anticancer Res ; 39(4): 1821-1827, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30952722

RESUMO

BACKGROUND/AIM: Ovarian cancer is the most frequent cause of death in women among gynecological cancers in Poland. MMP-2 and MMP-9 are frequently dysregulated in cancers and they are considered as potential biomarkers. Our goal was to assess the associations between MMP-2 and MMP-9 mRNA expression, clinicopathological parameters and patients' response to chemotherapy. MATERIALS AND METHODS: We evaluated MMP-2 and MMP-9 mRNA expression in epithelial ovarian cancer (EOC) tissues from 44 untreated patients, four ovarian cancer cell lines, and human skin fibroblasts (HSF). The expression of both MMPs was estimated using qPCR. RESULTS: MMP-2 expression was significantly higher (p=0.020) in EOCs sensitive to chemotherapy compared to resistant and refractory tumors. The highest MMP-2 expression was found in HSF and MMP-9 expression was the highest in EOCs (p<0.001). The expression of neither MMP was significantly associated with patients' overall survival (OS). CONCLUSION: MMP-2 may be engaged in early stages of ovarian carcinogenesis. MMP-2 expression in EOCs may discriminate patients with a favorable response to first line chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Carboplatina/administração & dosagem , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/genética , Metaloproteinase 2 da Matriz/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Paclitaxel/administração & dosagem , RNA Mensageiro/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Epitelial do Ovário/enzimologia , Carcinoma Epitelial do Ovário/mortalidade , Linhagem Celular Tumoral , Quimioterapia Adjuvante , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Humanos , Metaloproteinase 9 da Matriz/genética , Pessoa de Meia-Idade , Neoplasias Ovarianas/enzimologia , Neoplasias Ovarianas/mortalidade , Fatores de Tempo , Resultado do Tratamento
18.
Tumour Biol ; 41(4): 1010428319845749, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31014197

RESUMO

A role for matrix metalloproteinase polymorphisms in breast cancer development and progression was proposed, but with inconclusive results. We assessed the relation of matrix metalloproteinase-2 variants with breast cancer and related phenotypes in Tunisians. This case-control retrospective study involved 430 women with breast cancer and 498 healthy controls. Genotyping of matrix metalloproteinase-2 rs243866, rs243865, rs243864, and rs2285053 was analyzed by allelic exclusion. The minor allele frequency of rs2285053 was significantly lower in women with breast cancer cases as compared to control women; minor allele frequencies of the remaining single-nucleotide polymorphisms were similar between cases and control women. The distribution of rs243865 and rs2285053 genotypes was significantly different between breast cancer patients and control subjects. This persisted when key covariates were controlled for. None of the matrix metalloproteinase-2 variants were associated with estrogen receptor positivity, progesterone receptor positivity, or with double estrogen receptor-progesterone receptor positivity in breast cancer patients. Matrix metalloproteinase-2 rs243866, rs243865, and rs243864 were positively associated with menstrual irregularity and histological type, while rs243866 and rs2285053 were negatively associated with menarche and nodal status. In addition, rs2285053 was negatively associated with triple negativity, tumor size, distance metastasis, molecular type, and chemotherapy. Haploview analysis revealed high linkage disequilibrium between matrix metalloproteinase-2 variants. Four-locus Haploview analysis identified haplotypes GCTT and GTTC to be negatively associated with breast cancer, which remained statistically after controlling for key covariates. Matrix metalloproteinase-2 alleles and genotypes, along with four-locus haplotypes, are related to reduced susceptibility to breast cancer in Tunisian women, suggesting a protective effect.


Assuntos
Neoplasias da Mama/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Metaloproteinase 2 da Matriz/genética , Adulto , Alelos , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Feminino , Genótipo , Haplótipos , Humanos , Desequilíbrio de Ligação , Pessoa de Meia-Idade , Receptores de Progesterona/genética , Tunísia/epidemiologia
19.
Pharmazie ; 74(4): 243-249, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30940310

RESUMO

This study aimed to elucidate the roles and regulatory mechanism of miR-2861 in the development of endometriosis. The expression of miR-2861 in endometriotic tissues and eutopic endometrial tissues was determined. Ectopic endometrial cells were transfected with miR-2861 mimic, miR-2861 inhibitor and their corresponding controls. The effects of miR-2861 overexpression and inhibition on cell proliferation and apoptosis were then investigated. In addition, regulatory relationship between miR-2681 and signal transducer and activator of transcription 3 (STAT3) or matrix metalloproteinase 2 (MMP2) was explored, as well as between STAT3 and MMP2. Compared with eutopic endometrial tissues, miR-2861 was significantly downregulated in endometriotic tissues. Overexpression of miR-2861 markedly inhibited ectopic endometrial cell proliferation and induced apoptosis. Additionally, STAT3 and MMP2 were confirmed as the targets of miR-2861, and the effects of knockdown of STAT3 or MMP2on regulating cell proliferation and apoptosis were opposite with inhibition of miR-2861. Besides, STAT3 could enhance the expression of MMP2 in ectopic endometrial cells. Our study reveals that miR-2861 was lowly expressed in endometriotic tissues, and downregulation of miR-2861 may promote proliferation and inhibit apoptosis of ectopic endometrial cells in endometriosis via upregulation of STAT3 and MMP2. miR-2861 may be a potential biomarker or therapeutic target for endometriosis.


Assuntos
Endometriose/patologia , Metaloproteinase 2 da Matriz/genética , MicroRNAs/genética , Fator de Transcrição STAT3/genética , Adulto , Apoptose/genética , Proliferação de Células/genética , Células Cultivadas , Regulação para Baixo , Endometriose/genética , Endométrio/citologia , Endométrio/patologia , Feminino , Regulação da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos
20.
Mol Med Rep ; 19(6): 4964-4972, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30942419

RESUMO

Salidroside (SDS) is a phenylpropanoid glycoside isolated from Rhodiola rosea L. It exhibits multiple pharmacological properties in clinical medicine and has been commonly used in traditional Chinese medicine. The present study investigated the inhibitory effects of SDS on tumor invasion and migration, and the expression of metastasis­related genes in highly metastatic hepatocellular carcinoma (HCC) cells (MHCC97H) in vitro. The underlying mechanisms of SDS on the tumor metastasis were also explored. SDS was found to significantly reduce wound closure areas and inhibit cell migration. In addition, SDS markedly inhibited the invasion of these cells into Matrigel­coated membranes. SDS markedly downregulated the expression of Notch1, Snail, COX­2, MMP­2, MMP­9 genes and upregulated the expression of E­cadherin in a dose­dependent manner. Furthermore, SDS inhibited the expression of the Notch signaling target genes, Hey1, Hes1 and Hes5. On the whole, the findings of this study suggest that SDS inhibits HCC cell metastasis by modulating the activity of the Notch1 signaling pathway.


Assuntos
Glucosídeos/farmacologia , Fenóis/farmacologia , Receptor Notch1/metabolismo , Transdução de Sinais/efeitos dos fármacos , Caderinas/genética , Caderinas/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Regulação para Baixo/efeitos dos fármacos , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Receptor Notch1/antagonistas & inibidores , Fatores de Transcrição da Família Snail/genética , Fatores de Transcrição da Família Snail/metabolismo , Fatores de Transcrição HES-1/genética , Fatores de Transcrição HES-1/metabolismo
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