RESUMO
Vascular endothelial growth factor (VEGF) plays a crucial role in tumor angiogenesis. VEGF induces new vessel formation and tumor growth by inducing mitogenesis and chemotaxis of normal endothelial cells and increasing vascular permeability. However, little is known about VEGF function in the proliferation, survival or migration of hepatocellular carcinoma cells (HCC). In the present study, we have found that VEGF receptors are expressed in HCC line BEL7402 and human HCC specimens. Importantly, VEGF receptor expression correlates with the development of the carcinoma. By using a comprehensive approaches including TUNEL assay, transwell and wound healing assays, migration and invasion assays, adhesion assay, western blot and quantitative RT-PCR, we have shown that knockdown of VEGF165 expression by shRNA inhibits the proliferation, migration, survival and adhesion ability of BEL7402. Knockdown of VEGF165 decreased the expression of NF-κB p65 and PKCα while increased the expression of p53 signaling molecules, suggesting that VEGF functions in HCC proliferation and migration are mediated by P65, PKCα and/or p53.
Assuntos
Carcinoma Hepatocelular/patologia , Movimento Celular , Neoplasias Hepáticas/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Carcinoma Hepatocelular/enzimologia , Adesão Celular , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Humanos , Neoplasias Hepáticas/enzimologia , Invasividade Neoplásica , Proteína Quinase C-alfa/metabolismo , RNA Interferente Pequeno/metabolismo , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Proteína Supressora de Tumor p53/metabolismoRESUMO
OBJECTIVE: To study the inhibitory effect of extracts from Actinidia arguta by n-butyl alcohol on human carcinoma of esophagus cells (Eca-109) and Its mechanism. METHODS: MTT colonmetric assay was used to examine the growth inhibitory of concentration-effect (1 microg/ml, 10 microg/ml,100 microg/ml) and time-effect (24 h, 48 h, 72 h) of extracts from Actinidia arguta by n-butyl alcohol on Eca-109 cells. TUNEL test were performed to observe the apoptosis induced by the extracts (1 microg/ml, 10 microg/ml, 100 microg/ml) on Eca-109 cells. RESULTS: The inhibitory effect of the extracts on Eca-109 cells increased in a dose-time Manner and the highest rate of inhibition was 87.2%. The extracts could significantly induce apoptosis of Eca-109 cells, but in control group, apoptosis wasn't observed. CONCLUSION: The extracts from Actinidia arguta by n-butyl alcohol have good inhibitory effect on Eca-109 cells.
Assuntos
Actinidia/química , Antineoplásicos Fitogênicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Antineoplásicos Fitogênicos/administração & dosagem , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/administração & dosagem , Neoplasias Esofágicas/patologia , Humanos , Raízes de Plantas/química , Plantas Medicinais/química , Fatores de TempoRESUMO
TP53 and BRCA2 are frequently mutated in cancer and polymorphisms of these genes may modify cancer risk. We used SSCP and DNA sequencing to assess and compare frequencies of R72P (TP53) and 5'UTR203G>A, N372H, and K1132K (BRCA2) polymorphisms in healthy Chinese subjects at varying risk for esophageal squamous cell carcinoma (ESCC) and in ESCC patients. Suggestive overall differences in the distributions of genotypes by risk groups were seen for all genotypes except K1132K. Differences in R72P and N372H were most likely a reflection of lack of Hardy-Weinberg equilibrium (HWE), however, the difference in 203G>A was due to low prevalence of GG in ESCC patients (0.22 versus 0.36 in high risk group (P=0.047), and 0.22 versus 0.40 in low risk group (P=0.010)), consistent with a disease association. These data suggest that the 203G>A polymorphism in BRCA2 may be associated with risk of ESCC.