RESUMO
PURPOSE: Cervical cancer is one of the most prevalent malignancies in women worldwide. Therefore, the investigation about the molecular pathogenesis and related therapy targets of cervical cancer is an emergency. The objective of the present study is to investigate the effects of valproic acid (VPA), a histone deacetylase inhibitor, on the angiogenesis of cervical cancer. METHODS: The effects and mechanisms of VPA on in vitro angiogenesis and vascular endothelial growth factor (VEGF) expression of human cervical cancer HeLa and SiHa cells were investigated. RESULTS: Our present study reveals that 1 mM VPA can significantly inhibit the in vitro angiogenic potential and VEGF expression of human cervical cancer HeLa and SiHa cells. Further, the transcription and protein levels of hypoxia inducible factor-1α (HIF-1α), and not HIF-1ß, are significantly inhibited in VPA-treated cervical cancer cells. Over expression of HIF-1α can obviously reverse VPA-induced VEGF down regulation. VPA-treatment decreases the activation of Akt and ERK1/2 in both HeLa and SiHa cells in a time-dependent manner. The inhibitor of Akt (LY 294002) or ERK1/2 (PD98059) can inhibit VEGF alone and cooperatively reinforce the suppression effects of VPA on HIF-1α and VEGF expression. CONCLUSION: Collectively, our data reveal that the inhibition of PI3K/Akt and ERK1/2 signals are involved in VPA-induced HIF-1α and VEGF suppression of cervical cancer cells.
Assuntos
Inibidores da Angiogênese/farmacologia , Transdução de Sinais/efeitos dos fármacos , Neoplasias do Colo do Útero/patologia , Ácido Valproico/farmacologia , Western Blotting , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neovascularização Patológica/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Mitochondrial DNA mutations have been found to play important roles in carcinogenesis. The most common G10398A mutation, a non-conservative amino acid substitution from Thr to Ala, seems to be involved in the tumorigenesis of breast cancer. Results from studies concerning this mutation remain inconclusive. In the current study, we first took clinical and molecular datasets from case-control studies to determine the association between the G10398A mutation and breast cancer. We further used the Phylotree to determine the haplogroups of this mutation. The frequencies of this mutation in 500 unrelated healthy controls were also screened. We found that this mutation is very common in the human population, and may be a polymorph.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Carcinogênese , Complexo I de Transporte de Elétrons/genética , Substituição de Aminoácidos/genética , Neoplasias da Mama/patologia , Estudos de Casos e Controles , DNA Mitocondrial/genética , Feminino , Humanos , MutaçãoRESUMO
Helicobacter pylori strains may be either cagA+ or cagA-, and in logitudinal studies, infection with a cagA+ strain has been associated with increased risk for the development of atrophic gastritis and cancer of the distal stomach. We sought to determine the relative proportion of strains producing CagA in different geographic locales, and the extent to which CagA seroprevalence varied in countries with different gastric and esophageal cancer rates. Using an enzyme-linked immunosorbent assay (ELISA) to detect serum IgG to CagA, we examined sera from 468 asymptomatic H. pylori-infected adults from Canada, Peru, China, Thailand, The Netherlands and 3 different ethnic groups in New Zealand. The CagA seroprevalence in Peru and Thailand (82.2% and 78.8%, respectively) were each substantially higher than for the Chinese (37.9%), Canadian (41.9%), Dutch (39.0%) and New Zealand (28.2%) subjects, but within each population, rates were relatively constant across gender and age groups. Reported gastric but not esophageal cancer rates for the 8 studied populations were significantly associated with H. pylori seroprevalence. Variation in CagA positivity rates was not significantly associated with variation in either gastric or esophageal cancer rates. Our data suggest that CagA seroprevalence is not the major factor influencing gastric cancer rates.