ABSTRACT
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.
Subject(s)
Carcinoma, Hepatocellular/pathology , Cell Movement , Liver Neoplasms/pathology , Vascular Endothelial Growth Factor A/metabolism , Carcinoma, Hepatocellular/enzymology , Cell Adhesion , Cell Line, Tumor , Cell Proliferation , Cell Survival , Humans , Liver Neoplasms/enzymology , Neoplasm Invasiveness , Protein Kinase C-alpha/metabolism , RNA, Small Interfering/metabolism , Receptors, Vascular Endothelial Growth Factor/metabolism , Tumor Suppressor Protein p53/metabolismABSTRACT
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.
Subject(s)
Actinidia/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Cell Proliferation/drug effects , Drugs, Chinese Herbal/pharmacology , Antineoplastic Agents, Phytogenic/administration & dosage , Apoptosis/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Dose-Response Relationship, Drug , Drugs, Chinese Herbal/administration & dosage , Esophageal Neoplasms/pathology , Humans , Plant Roots/chemistry , Plants, Medicinal/chemistry , Time FactorsABSTRACT
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.
