Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 56
Filtrar
Mais filtros










Base de dados
Tipo de estudo
Intervalo de ano de publicação
1.
Biomed Pharmacother ; 127: 110215, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32413671

RESUMO

The pathogenesis and tumorigenesis of clear cell renal cell carcinoma (ccRCC) remain unclear. The deregulations of miR-429, a member of miR-200 family, and v-crk sarcoma virus CT10 oncogene homologue (avian)-like (CRKL), an adaptor protein of CRK family, are involved in the development, metastasis and prognosis of various cancers. Current study aimed to demonstrate the differential expressions of miR-429 and CRKL with their correlationship and molecular regulation mechanism in ccRCC malignancy. miR-429 and CRKL separately showed suppressing and promoting effects in ccRCC. Lower miR-429 expression and higher CRKL expression were negatively correlated in surgical cancerous tissues by promoting the advance of ccRCC. By binding to the 3'-UTR of CRKL, miR-429 reversely regulated CRKL for its functionalities in ccRCC cells. CRKL knockdown and overexpression separately decreased and increased the in vitro migration and invasion of 786-O cells, which were consistent with the influences of miR-429 overexpression and knockdown on 786-O through respectively downregulating and upregulating CRKL via SOS1/MEK/ERK/MMP2/MMP9 pathway. The enhancements of CRKL expression, migration and invasion abilities and SOS1/MEK/ ERK/MMP2/MMP9 activation induced by TGF-ß stimulation in 786-O cells could be antagonized by miR-429 overexpression. Exogenous re-expression of CRKL abrogated miR-429 suppression on the migration and invasion of 786-O cells. Collectively, miR-429 deficiency negatively correlated with CRKL overexpression promoted the aggressiveness of cancer cells and advanced the clinical progression of ccRCC patients. miR-429-CRKL axial regulation provides new clues to the fundamental research, diagnosis and treatment of ccRCC.

2.
BMB Rep ; 53(4): 240, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32340662

RESUMO

[Erratum to: BMB Reports 2010; 43(8): 554-560, PMID: 20797318] The authors apologize that due to our neglect when doing the picture layout of Fig. 1A, the wrong Western blot analysis image were pasted for the "ß-actin"group in the middle plot of Fig. 1A. The middle plot of Fig. 1A and its related statistics results (bottom plot in Fig.1A) have been corrected. However, the conclusions of the original article are not affected. The authors would like to apologize for any inconvenience caused.

3.
J Exp Clin Cancer Res ; 39(1): 70, 2020 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-32326970

RESUMO

BACKGROUND: Tumor metastasis is one of the main causes of the high mortality of hepatocellular carcinoma (HCC). E-Twenty Six variant gene 6 (ETV6) is a strong transcriptional repressor, associated with the development and progression of tumors. However, the exact role and underlying mechanism of ETV6 in HCC remain unclear. METHODS: Western blotting, quantitative real-time PCR and immunohistochemistry were used to detect the expression levels of ETV6, CRKL (v-crk sarcoma virus CT10 oncogene homologue (avian)-like) and miR-429 in HCC tissues and cells; Transwell chamber and F-actin cytoskeleton staining assay to examine the effects of ETV6 and CRKL deregulation on the migration, invasion and cytoskeleton of HCC cells; Co-immunoprecipitation assay to determine the interaction between CRKL and ETV6; Chromatin immunoprecipitation assay to investigate the interaction between ETV6 and miR-429. RESULTS: We established a novel ETV6-miR-429-CRKL regulatory circuitry contributes to HCC metastasis. ETV6 and CRKL were frequently increased, while miR-429 was downregulated in both hepatocarcinoma tissues and hepatocarcinoma cells. Moreover, ETV6 upregulation was positively correlated with CRKL upregulation, and two negative correlations were also established for ETV6 and CRKL upregulation with miR-429 downregulation in both hepatocarcinoma patients' tumorous tissues and hepatocarcinoma cells. Functional investigations revealed that overexpression and knockdown of ETV6 was remarkably effective in promoting and suppressing HCC cell migration, invasion, cytoskeleton F-actin expression and arrangement, whereas, CRKL overexpression exhibited similar effects to the overexpression of ETV6. Mechanistically, ETV6 negatively regulates miR-429 expression by directly binding to the promoter region of miR-429; miR-429 negatively regulates CRKL expression by selectively targeting CRKL-3'-UTR; ETV6 directly binds to CRKL and positively regulates its expression, which in turn CRKL positively regulates ETV6 expression. CONCLUSIONS: Our data demonstrated that ETV6 promotes migration and invasion of HCC cells by directly binding to promoter region of miR-429 via modulating CRKL expression. The newly identified ETV6-miR-429-CRKL regulatory circuitry contributes to the aggressiveness of HCC, which provides new clues for fundamental research on diagnosis and treatment parameters for HCC.

4.
Oncol Lett ; 17(6): 5169-5174, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31186732

RESUMO

Lymphatic metastasis is a major mechanism of tumor metastasis. The present study aimed to investigate the association of CRKII, a member of the CRK family, with the in vitro malignant behaviors of a murine hepatocarcinoma Hca-P cell line, with a lymph node metastatic rate of ~25%. Total mRNA was extracted from Hca-P cells, and then the murine CRKII gene was amplified by polymerase chain reaction and cloned into the pEASY-blunt cloning vector. Subsequently, the recombinant pcDNA3.1/V5-HisB-CRKII plasmid was constructed and transfected into Hca-P cells. Western blotting indicated that the CRKII expression level in pcDNA3.1/V5-HisB-CRKII-Hca-P cells was increased by ~185%, compared with pcDNA3.1/V5-HisB-Hca-P cells. The stable overexpression of CRKII enhanced the in vitro proliferation ability, as measured with a Cell Counting Kit-8 assay, and the colony forming capacity was measured with a soft agar colony forming assay for Hca-P cells. The in vitro migration and invasion capacities of Hca-P cells were increased by ~179 and 156% in Hca-P cells, respectively, following the stable upregulation of CRKII. Collectively, the recombinant pcDNA3.1/V5-HisB-CRKII-Hca-P plasmid was constructed successfully. Additionally, the CRKII expression level was positively associated with the in vitro proliferation, migration and invasion malignant properties of Hca-P cells.

5.
Cell Death Discov ; 5: 89, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31016032

RESUMO

Clear cell renal cell carcinoma (ccRCC) is the most aggressive RCC subtype with high metastasis, chemotherapy and radiotherapy resistance, and poor prognosis. This study attempted to establish the deregulations of miR-4521 and FAM129A together with their correlation to and mechanism of regulation of ccRCC development and progression. FAM129A acted as tumor promotor and miR-4521 acted as a suppressor in ccRCC. As measured in surgical tumorous tissues from ccRCC patients, FAM129A overexpression and miR-4521 deficiency together contributed to ccRCC progression by promoting advances in patients' TNM stage and Fuhrman grade. Both the FAM129A knockdown and miR-4521 overexpression could reduce the in vitro migration and invasion abilities of renal cancer cells 786-O and ACHN, through the TIMP-1/MMP2/MMP9 pathway and could decrease their proliferation by promoting their apoptosis through the MDM2/p53/Bcl2/Bax pathway. By directly targeting the 3'-UTR domain of FAM129A, miR-4521 was negatively correlated with FAM129A/FAM129A levels in ccRCC progression and renal cancer cell malignancies. This work establishes the miR-4521-FAM129A axial regulation mechanism in ccRCC. Micro-4521 deficiency leads to FAM129A/FAM129A upregulation, which synergistically enhances the migration and invasion of renal cancer cells due to the induced decrease of TIMP-1 and increases of MMP2 and MMP9, and increases their growth through escaping apoptosis by suppressing p53 by way of upregulation of induced MDM2. The current work provides new clues to assist fundamental research into the diagnosis and treatment of ccRCC.

6.
Cell Death Dis ; 9(6): 637, 2018 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-29802377

RESUMO

As a calcium-dependent phospholipid binding annexin protein, annexin A5 (Anxa5) links to the progression, metastasis, survival, and prognosis of a variety of cancers. Current work showed ANXA5 overexpression was positively correlated with the upregulations of CRKI/II and RAC1 in hepatocarcinoma (HCC) patients' tissues, which potentially enhanced the clinical progression and lymphatic metastasis of HCC. The role and action mechanism of ANXA5 in hepatocarcinoma was then investigated using a hepatocarcinoma Hca-P cell line, an ideal and well-established murine cell model with 100% inducible tumorigenicity of implanted mice with low (~25%) lymph node metastatic (LNM) rate. In vitro evidences indicated ANXA5 stable knockdown resulted in decreased proliferation, migration, invasion and adhesion to lymph node (LN), and increased intercellular cohesion behaviors of hepatocarcinoma Hca-P cells. Consistently, stable ANXA5 knockdown led to reduced in vivo tumorigenicity and malignancy, LNM rate and level potentials of Hca-P- transplanted mice via inhibiting CD34 and VEGF3. The levels of CRKI/II and RAC1 were reduced in tumor tissues from mice transplanted with Hca-P cells with stable ANXA5 knockdown. Molecular action investigation further showed ANXA5 downregulation apparently suppressed the expressions of molecules CRKI/II, DOCK180, RAC1 in integrin pathway, p-MEK, p-ERK, c-Myc, and MMP-9 in MEK- ERK pathway together with VIMINTIN in Hca-P cells in appropriate to knockdown extent. Collectively, Anxa5 was able to mediate HCC carcinogenesis via integrin and MEK-ERK pathways. It is of potential use in the research and treatment of HCC.


Assuntos
Anexina A5/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Sistema de Sinalização das MAP Quinases , Animais , Antígenos CD34/metabolismo , Carcinogênese/patologia , Adesão Celular , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Regulação para Baixo , Feminino , Humanos , Metástase Linfática , Masculino , Camundongos , Pessoa de Meia-Idade , Modelos Biológicos , Invasividade Neoplásica , Metástase Neoplásica , Proteínas Proto-Oncogênicas c-crk/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Proteínas rac de Ligação ao GTP/metabolismo , Proteínas rac1 de Ligação ao GTP/metabolismo
7.
Sci Rep ; 8(1): 2375, 2018 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-29403024

RESUMO

Tumor metastasis is one of the main causes of hepatocellular carcinoma (HCC) high mortality. CRKL (v-crk sarcoma virus CT10 oncogene homologue (avian)-like) play important roles in tumor metastasis, however, the exact role and underlying mechanism of CRKL in HCC is still unknown. In our study, we demonstrated miR-429 negatively regulated CRKL expression via selectively binding to CRKL-3'-UTR at 3728-3735 bp site by post-transcriptionally mediating its functionality. Re-expression and silencing of miR-429 was remarkably effective in suppressing and promoting HepG2 cell migration and invasion in vitro. Knockdown or overexpression of CRKL exhibited similar effects as the overexpression or silencing of miR-429, whereas, CRKL overexpression (without the 3'-UTR) abrogated miR-429-induced inhibition on HepG2 migration and invasion. Moreover, miR-429-CRKL axis affected HepG2 migration and invasion potentials by regulating the adhesion ability, cytoskeleton F-actin expression and arrangement of HepG2. Furthermore, interference of Raf/MEK/ERK pathway and EMT contributed to miR-429-CRKL axis mediated metastasis inhibition. Nevertheless, miR-429 could not inhibit HepG2 proliferation through CRKL/c-Jun pathway. Taken together, our data demonstrated that miR-429 might function as an antimetastatic miRNA to regulate HCC metastasis by directly targeting CRKL via modulating Raf/MEK/ERK-EMT pathway. The newly identified miR-429-CRKL axis represents a novel potential therapeutic target for HCC treatment.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Carcinoma Hepatocelular/secundário , Transição Epitelial-Mesenquimal , Sistema de Sinalização das MAP Quinases , MicroRNAs/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Proteínas Nucleares/metabolismo , Quinases raf/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
8.
Clin Chim Acta ; 476: 98-102, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29174342

RESUMO

BACKGROUND: Higher fetuin-A expression is linked to both obesity and type 2 diabetes mellitus (T2DM), However, studies in non-obese patients with T2DM are scarce. METHODS: 345 newly diagnosed T2DM patients and 300 subjects with normal glucose tolerance (NGT) were divided into obese and non-obese subgroups, respectively. Serum fetuin-A and adiponectin levels and related parameters were measured. RESULTS: T2DM patients with obesity had higher fetuin-A levels compared with non-obese patients and obese NGT subjects (p<0.001). Significant correlations were observed between fetuin-A and most metabolic parameters in obese NGT and T2DM subjects, but which was not in non-obese patients with T2DM. The independent associations were found between fetuin-A and free fatty acids, HOMA-IR, C-reactive protein and adiponectin only in obese NGT and T2DM subjects (all p<0.05). The adjusted odds ratios for obesity were increased with increasing quartile of fetuin-A in both T2DM and NGT subjects in logistic regression models (p for trend<0.001), but which was more significant in T2DM patients. CONCLUSION: Higher serum fetuin-A levels in obese T2DM patients compared with non-obese patients and obese NGT subjects supports the hypothesis that fetuin-A may be as a bridge connecting obesity and obesity-related T2DM.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Obesidade/sangue , alfa-2-Glicoproteína-HS/análise , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
9.
Biomed Pharmacother ; 84: 645-654, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27697636

RESUMO

OBJECTIVE: Annexin A5 (Anxa5) is associated with the progression of some cancers, while its role and regulation mechanism in tumor lymphatic metastasis is rarely reported. This study aims to investigate the influence of Anxa5 knockdown on the malignant behaviours of murine hepatocarcinoma Hca-F cell line with high lymph node metastatic (LNM) potential and the underlying regulation mechanism. METHODS: RNA interfering was performed to silence Anxa5 in Hca-F. Monoclonal shRNA-Anxa5- Hca-F cells were obtained via G418 screening by limited dilution method. Quantitative real-time RT-PCR (qRT-PCR) and Western blotting (WB) were applied to measure Anxa5 expression levels. CCK-8, Boyden transwell-chamber and in situ LN adhesion assays were performed to explore the effects of Anxa5 on the proliferation, migration, invasion and adhesion capacities of Hca-F. WB and qRT-PCR were used to detect the level changes of key molecules in corresponding signal pathways. RESULTS: We obtained two monoclonal shRNA-Anxa5-transfected Hca-F cell lines with stable knockdowns of Anxa5. Anxa5 knockdown resulted in significantly reduced proliferation, migration, invasion and in situ LN adhesion potentials of Hca-F in proportion to its knockdown extent. Anxa5 downregulation enhanced E-cadherin levels in Hca-F. Moreover, Anxa5 affected Hca-F behaviours specifically via ERK2/p-ERK2/c-Jun/p-c-Jun(Ser73) instead of p38MAPK/c-Jun, Jnk/c-Jun and AKT/c-Jun pathways. CONCLUSIONS: Anxa5 mediates the in vitro malignant behaviours of murine hepatocarcinoma Hca-F cells via ERK2/c-Jun/p-c-Jun(Ser73) and ERK2/E-cadherin pathways. It is an important molecule in metastasis (especially LNM) and a potential therapeutic target for hepatocarcinoma.


Assuntos
Anexina A5/metabolismo , Caderinas/metabolismo , Carcinoma Hepatocelular/enzimologia , Neoplasias Hepáticas Experimentais/enzimologia , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteínas Proto-Oncogênicas c-jun/metabolismo , Animais , Anexina A5/genética , Antígenos CD , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/secundário , Adesão Celular , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas Experimentais/genética , Neoplasias Hepáticas Experimentais/patologia , Metástase Linfática , Camundongos , Fosforilação , Interferência de RNA , Transdução de Sinais , Fatores de Tempo , Transfecção
10.
Clin Chim Acta ; 455: 113-7, 2016 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-26851648

RESUMO

BACKGROUND: The higher expression of vascular endothelial growth factor (VEGF) and C-reactive protein (CRP) is associated with the development of diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM). Fetuin-A is shown to have proangiogenic and proinflammatory effects. METHODS: This study included 245 T2DM patients consisting of 95 cases with non-diabetic retinopathy (NDR), 78 cases with non-proliferative diabetic retinopathy (NPDR) and 72 cases with proliferative diabetic retinopathy (PDR), in addition to 65 healthy controls. Serum fetuin-A, VEGF and CRP concentrations and related parameters were measured. RESULTS: Significant positive correlations were found between fetuin-A and VEGF and CRP, and between VEGF and CRP in T2DM patients (all p<0.001). After adjustment for confounders, fetuin-A was correlated independently with VEGF and CRP in NPDR and PDR patients, but not in NDR subjects. In addition, fetuin-A was correlated independently with HOMA-IR (all 4 groups), HbA1c (NDR, NPDR and PDR groups) and duration of diabetes (PDR group). When compared with NDR and control subjects, NPDR and PDR patients had higher HOMA-IR. CONCLUSIONS: Serum fetuin-A concentrations are independently correlated with VEGF and CRP concentrations in T2DM patients with DR, but not in NDR subjects.


Assuntos
Proteína C-Reativa/metabolismo , Diabetes Mellitus Tipo 2/complicações , Fator A de Crescimento do Endotélio Vascular/sangue , alfa-2-Glicoproteína-HS/metabolismo , Idoso , Nefropatias Diabéticas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
11.
Oncotarget ; 7(13): 16297-310, 2016 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-26908448

RESUMO

Annexin A11 (Anxa11) is associated with various cancers. Using a pair of syngeneic murine hepatocarcinoma cells, Hca-P with ~25% and Hca-F with ~75% lymph node metastatic (LNM) potentials, we demonstrated Anxa11 involvement in hepatocarcinoma lymphatic metastasis. Here, ANXA11 acted as a suppressor for the tumorigenicity, LNM and 5-FU resistance of Hca-P via c-Jun. We constructed monoclonal Hca-P cell line with stable ANXA11 knockdown. Although Bax and Bcl-2 levels increased in shRNA-Anxa11-transfected Hca-P, ANXA11 downregulation showed no clear effect on Hca-P apoptosis. ANXA11 downregulation promoted in vitro migration and invasion capacities of Hca-P. In situ adhesion potential of Hca-P cells toward LN was significantly enhanced following ANXA11 downregulation. Consistently, ANXA11 downregulation promoted the in vivo tumor growth and LNM capacities of Hca-P cells. ANXA11 knockdown enhanced the chemoresistance of Hca-P cells specifically toward 5-FU instead of cisplatin. Its downregulation increased c-Jun (pSer73) and decreased c-Jun (pSer243) levels in Hca-P. c-Jun (pSer243) downregulation seemed to be only correlated with ANXA11 knockdown without the connection to 5-FU treatment. Interestingly, compared with scramble-Hca-P cells, the levels of c-Jun and c-Jun (pSer73) in shRNA-Anxa11-Hca-P cells were upregulated in the presences of 0.1 and 1.0 mg/L 5-FU. The levels changes from c-Jun and c-Jun (pSer73) in Hca-P cells showed a more obvious tendency with the combination of ANXA11 knockdown and 5-FU treatment. ANXA11 level regulates LNM and 5-FU resistance of Hca-P via c-Jun pathway. It might play an important role in hepatocarcinoma cell malignancy and be a therapeutic target for hepatocarcinoma.


Assuntos
Anexinas/metabolismo , Carcinoma Hepatocelular/patologia , Resistencia a Medicamentos Antineoplásicos/fisiologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Neoplasias Hepáticas/patologia , Metástase Linfática/patologia , Animais , Antineoplásicos/farmacologia , Carcinogênese/metabolismo , Carcinogênese/patologia , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Fluoruracila/farmacologia , Neoplasias Hepáticas/metabolismo , Camundongos
12.
Future Oncol ; 12(1): 31-42, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26615672

RESUMO

AIM: To investigate ANXA5 overexpression on in vitro and in vivo malignancies of murine Hca-P cells. MATERIALS & METHODS: Hca-P with low lymph node metastasis (LNM) potential was used as cell model. TEM, CCK-8 and Boyden transwell assays were performed for in vitro Hca-P behaviors. Hca-P-transplanted mouse model was established for in vivo experiment. RESULTS: ANXA5-overexpressing monoclonal Anxa5-Hca-P-1, Anxa5-Hca-P-2 and Anxa5-Hca-P-3 cells were obtained. ANXA5 upregulation alters the proliferation, morphology and rough endoplasmic reticulum of Hca-P cells, enhances in vitro migration and invasions of Hca-P, promotes in vivo malignant degree and LNM rate of Anxa5-Hca-P-3-transplanted mice. CONCLUSION: As a potential indicator for malignancy and lymphatic metastasis, ANXA5 overexpression increases in vitro migration and invasion of Hca-P cell, promotes in vivo malignancy, LNM rate and level of Hca-P-transplanted mice.


Assuntos
Anexina A5/biossíntese , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Metástase Linfática/genética , Animais , Anexina A5/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Modelos Animais de Doenças , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/patologia , Metástase Linfática/patologia , Camundongos , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia
13.
Sci Rep ; 5: 18215, 2015 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-26655928

RESUMO

Previously, we characterized the biological properties of Akbu-LAAO, a novel L-amino acid oxidase from Agkistrodon blomhoffii ussurensis snake venom (SV). Current work investigated its in vitro anti-tumor activity and underlying mechanism on HepG2 cells. Akbu-LAAO inhibited HepG2 growth time and dose-dependently with an IC50 of ~38.82 µg/mL. It could induce the apoptosis of HepG2 cells. Akbu-LAAO exhibited cytotoxicity by inhibiting growth and inducing apoptosis of HepG2 as it showed no effect on its cell cycle. The inhibition of Akbu-LAAO to HepG2 growth partially relied on enzymatic-released H2O2 as catalase only partially antagonized this effect. cDNA microarray results indicated TGF-ß signaling pathway was linked to the cytotoxicity of Akbu-LAAO on HepG2. TGF-ß pathway related molecules CYR61, p53, GDF15, TOB1, BTG2, BMP2, BMP6, SMAD9, JUN, JUNB, LOX, CCND1, CDK6, GADD45A, CDKN1A were deregulated in HepG2 following Akbu-LAAO stimulation. The presence of catalase only slightly restored the mRNA changes induced by Akbu-LAAO for differentially expressed genes. Meanwhile, LDN-193189, a TGF-ß pathway inhibitor reduced Akbu-LAAO cytotoxicity on HepG2. Collectively, we reported, for the first time, SV-LAAO showed anti-tumor cell activity via TGF-ß pathway. It provides new insight of SV-LAAO exhibiting anti-tumor effect via a novel signaling pathway.


Assuntos
Antineoplásicos/farmacologia , Peróxido de Hidrogênio/metabolismo , L-Aminoácido Oxidase/farmacologia , Transdução de Sinais/efeitos dos fármacos , Venenos de Serpentes/química , Fator de Crescimento Transformador beta/metabolismo , Apoptose/efeitos dos fármacos , Catalase/metabolismo , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Hep G2 , Humanos
14.
Oncol Lett ; 10(4): 1947-1952, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26622779

RESUMO

Annexin A6 (AnxA6) is a member of a conserved superfamily of Ca2+-dependent membrane-binding annexin proteins. It participates in membrane and cytoskeleton organization, cholesterol homeostasis, membrane trafficking, cell adhesion and signal transduction. The expression levels of AnxA6 are closely associated with melanoma, cervical cancer, epithelial carcinoma, breast cancer, gastric cancer, prostate cancer, acute lymphoblastic leukemia, chronic myeloid leukemia, large-cell lymphoma and myeloma. AnxA6 exhibits dual functions in cancer, acting either as a tumor suppressor or promoter, depending on the type of cancer and the degree of malignancy. In several types of cancer, AnxA6 acts via Ras, Ras/MAPK and/or FAK/PI3K signaling pathways by mainly mediating PKCα, p120GAP, Bcr-Abl and YY1. In the present review, the roles of AnxA6 in different types of cancer are summarized.

15.
Biochimie ; 116: 34-42, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26133656

RESUMO

Adinbitor is a disintegrin previously obtained from Agkistrodon halys brevicaudus stejneger by our group. Here, we investigated the in vitro and in vivo anti-tumor activities of recombinant Adinbitor (rAdinbitor). rAdinbitor stimulation can inhibit the in vitro proliferation, migration and invasion capacities of murine hepatocarcinoma H22 and Hca-F cells. The administrations of rAdinbitor either by gavage or intraperitoneal injection suppress the tumor malignancy and prolong the survival rate and time of H22-transplanted mice. The number and size of formed blood vessels decreased dramatically in tumorous tissues in that the expression levels of vascular endothelial growth factor (VEGF) and cluster of differentiation 34 (CD34) were significantly decreased in responding to rAdinbitor treatment. The protein levels of IL-18 and IgG increased significantly in the serum of H22-transplanted tumor mice with rAdinbitor treatment. rAdinbitor shows in vitro and in vivo anti-tumor effects as an angiogenesis inhibitor and immunocompetence enhancer.


Assuntos
Agkistrodon/metabolismo , Desintegrinas/farmacologia , Desintegrinas/uso terapêutico , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Desintegrinas/química , Imunocompetência , Neoplasias Hepáticas/tratamento farmacológico , Camundongos
16.
Clin Chim Acta ; 447: 72-8, 2015 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-26048190

RESUMO

Annexin A4 (Anxa4) is one of the Ca(2+)-regulated and phospholipid-binding annexin superfamily proteins. Anxa4 has a potential role in diagnosis, prognosis, and treatment of certain cancers. Studies indicate that Anxa4 up-regulation promotes the progression of tumor and chemoresistance of colorectal cancer (CRC), esophageal squamous cell carcinoma (ESCC), endometrial carcinoma (EC), gastric cancer (GC), chemoresistant lung cancer (LC), malignant mesothelioma (MM), renal cell carcinoma (RCC), ovarian clear cell carcinoma (OCCC), cholangiocarcinoma, hepatocellular carcinoma (HCC), breast cancer (BC), and laryngeal cancer. Interestingly, Anxa4 also might specifically function as a tumor suppressor for prostate cancer (PCa) and have a paradoxical role for pancreatic cancer (PCC). Differential expression of Anxa4 may distinguish major salivary gland tumor (MSGT) from thyroid cancer. In addition, its differential expression was linked to Sirt1-induced cisplatin resistance of oral squamous cell carcinoma (OSCC) and miR-7-induced migration and invasion inhibition of glioma. This current review summarizes and discusses the clinical significance of Anxa4 in cancer as well as its potential mechanisms of action. It may provide new integrative understanding for future studies on the exact role of Anxa4 in cancer.


Assuntos
Anexina A4/metabolismo , Neoplasias/metabolismo , Humanos
17.
Biomed Pharmacother ; 71: 84-90, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25960220

RESUMO

Our previous study (Biomed Pharmacother 2015;69:11) demonstrated that the over-expression of CRKL, a chicken tumor virus number 10 regulator of kinase-like protein, suppresses in vitro proliferation, invasion and migration of murine hepatocarcinoma Hca-P cell, a murine HCC cell with lymph node metastatic (LNM) rate of ∼25%. In current work, we investigated the effects of CRKL knockdown on the in vitro cell proliferation, migration and invasion, and on the in vivo tumor malignancy and LNM rate and level for Hca-P cells. Western blotting assay indicated that CRKL was down-regulated by ∼90% in a monoclonal CrkL-shRNA-transfected Hca-P cells. Compared with Hca-P and unrelated-shRNA-transfected Hca-P cell, the in vitro proliferation, migration and invasion potentials were significantly enhanced following CRKL stable deregulation. CRKL knock-down significantly promoted the tumorigenicity malignancy, LNM rates and level of Hca-P-transplanted mice. Consistent with our previous work, it can be concluded CRKL plays an important role in hepatocarcinoma cell proliferation, invasion and migration as well hepatocarcinoma malignancy and metastasis. It functions as a potential tumor suppressor in hepatocarcinoma.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Movimento Celular , Técnicas de Silenciamento de Genes , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Metástase Linfática/patologia , Proteínas Nucleares/metabolismo , Animais , Carcinogênese/patologia , Linhagem Celular Tumoral , Proliferação de Células , Regulação para Baixo , Camundongos , Invasividade Neoplásica , Transplante de Neoplasias , RNA Interferente Pequeno/metabolismo , Transfecção
18.
Biomed Pharmacother ; 70: 58-63, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25776480

RESUMO

Annexin A11 (Anxa11), a Ca(2+)-regulated phospholipid-binding protein, is involved in cell apoptosis, differentiation, vesicle trafficking, cancer progression and autoimmune diseases. Previous study from our group indicated that Anxa11 was associated with lymphatic metastatic potential of murine hepatocarcinoma cells. Herein, we investigated the effects and action mechanism of Anxa11 knockdown on in vitro cell proliferation and apoptosis of Hca-F, a murine hepatocarcinoma cell with∼75% lymph node metastatic potential. Real-time PCR and western blotting assays indicated that Anxa11 was significantly downregulated in monoclonal Anxa11-shRNA-transfected Hca-F cells. Anxa11 knockdown in Hca-F suppressed its in vitro proliferation and cell apoptosis capacities. Following Anxa11 knockdown in Hca-F cells, Bax/Bcl-2 expression level ratio, Akt2 and FoxO1 (pSer319) expression levels as well as MMP-9 mRNA and active MMP-9 protein levels were significantly elevated in Hca-F cells. In conclusion, Annexin A11 knockdown inhibits the in vitro proliferation and cell apoptosis of Hca-F cell via Akt2/FoxO1 and/or MMP-9 expression pathway. Anxa11 might play an important role in hepatocarcinoma cell invasion and metastasis and hepatocarcinoma malignancy.


Assuntos
Anexinas/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Anexinas/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Proteína Forkhead Box O1 , Fatores de Transcrição Forkhead/genética , Regulação Neoplásica da Expressão Gênica/fisiologia , Técnicas de Silenciamento de Genes , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Metaloproteinase 9 da Matriz/genética , Camundongos , Proteínas Proto-Oncogênicas c-akt/genética
19.
Biomed Pharmacother ; 69: 11-7, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25661331

RESUMO

The signal adaptor CRK family protein play important roles in cancer cell progression, proliferation, migration and invasion. Previously, we showed that CRK was involved in lymphatic metastatic potential of murine hepatocarcinoma cells. In current work, as a member of CRK family, chicken tumour virus number 10 regulator of kinase-like protein (CRKL) was revealed to be associated with malignant behaviors of Hca-P, a murine HCC cell with lymph node metastatic (LNM) rate of ∼25%. CRKL overexpression in Hca-P by a constructed eukaryotic expression vector of pcDNA3.1/V5-HisB-CRKL significantly ameliorated its malignant biological properties. CCK-8 and soft agar colony formation assays indicated CRKL overexpression significantly inhibits the cell proliferation and colony formation abilities of Hca-P. Additionally, transwell assays indicated that the Hca-P cell migration and invasion capacities were apparently reduced following CRKL overexpression. As Hca-P is an ideal hepatocarcinoma cell model with low (initial) LNM potential, CRKL is shown to act as a potential suppressor and to provide new insight for both the malignant behaviors of hepatocarcinoma cells and lymphatic metastasis mechanism of hepatocarcinoma.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Movimento Celular , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Proteínas Nucleares/metabolismo , Animais , Sequência de Bases , Linhagem Celular Tumoral , Proliferação de Células , Camundongos , Dados de Sequência Molecular , Invasividade Neoplásica , Plasmídeos/metabolismo , Transfecção , Ensaio Tumoral de Célula-Tronco , Regulação para Cima
20.
Int J Clin Exp Med ; 8(10): 19014-21, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26770527

RESUMO

An effective blood test is valuable to aid clinicians in making case management decisions. The present study was to analyze the value of four serum tumor markers for the diagnosis of pulmonary carcinoma. The case group consisted of 80 pulmonary carcinoma patients, which were compared to a control group of 30 patients with benign pulmonary disease and a control group of 30 healthy individuals. Serum levels of carcinoma embryonic antigen (CEA), cytokeratin protein fragment 21-1 (CYFRA21-1), neuron-specific enolase (NSE), and human epididymis protein 4 (HE4) were detected using electrochemiluminescence. Serum CEA, NSE, CYFRA21-1, and HE4 levels were significantly higher in pulmonary carcinoma patients than those in both control groups (P < 0.05). Serum CEA and HE4 levels were significantly higher in adenocarcinoma patients, while serum CYFRA21-1 levels were significantly higher in squamous cell carcinoma patients and serum NSE levels were significantly higher in small cell lung cancer (SCLC) patients (P < 0.05). Analysis of area-under-the-receiver operating characteristic (ROC) curves (AUC) revealed that serum CYFRA21-1, CEA, and HE4 levels were valuable for squamous cell carcinoma, serum CEA and HE4 levels were valuable for adenocarcinoma, and serum NSE level was valuable for SCLC (P < 0.05). Serum CEA and HE4 levels of pulmonary carcinoma patients with metastasis were higher than those with TNM stage I-II or III-IV disease without metastasis. In brief, detection of serum HE4 levels may be useful in auxiliary diagnosis and evaluation of the progression of pulmonary carcinoma.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA