RESUMO
Substantial data from preclinical studies have revealed the biphasic effects of statins on cardiovascular angiogenesis. Although some have reported the anti-angiogenic potential of statins in malignant tumors, the underlying mechanism remains poorly understood. The aim of this study is to elucidate the mechanism by which simvastatin, a member of the statin family, inhibits tumor angiogenesis. Simvastatin significantly suppressed tumor cell-conditioned medium-induced angiogenic promotion in vitro, and resulted in dose-dependent anti-angiogenesis in vivo. Further genetic silencing of hypoxia-inducible factor-1α (HIF-1α) reduced vascular endothelial growth factor and fibroblast growth factor-2 expressions in 4T1 cells and correspondingly ameliorated HUVEC proliferation facilitated by tumor cell-conditioned medium. Additionally, simvastatin induced angiogenic inhibition through a mechanism of post-transcriptional downregulation of HIF-1α by increasing the phosphorylation level of AMP kinase. These results were further validated by the fact that 5-aminoimidazole-4-carboxamide ribonucleotide reduced HIF-1α protein levels and ameliorated the angiogenic ability of endothelial cells in vitro and in vivo. Critically, inhibition of AMPK phosphorylation by compound C almost completely abrogated simvastatin-induced anti-angiogenesis, which was accompanied by the reduction of protein levels of HIF-1α and its downstream pro-angiogenic factors. These findings reveal the mechanism by which simvastatin induces tumor anti-angiogenesis, and therefore identifies the target that explains the beneficial effects of statins on malignant tumors.
Assuntos
Proteínas Quinases Ativadas por AMP/fisiologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/fisiologia , Neovascularização Patológica/prevenção & controle , Sinvastatina/farmacologia , Proteínas Quinases Ativadas por AMP/antagonistas & inibidores , Animais , Linhagem Celular Tumoral , Proliferação de Células , Relação Dose-Resposta a Droga , Ativação Enzimática/efeitos dos fármacos , Feminino , Fator 2 de Crescimento de Fibroblastos/análise , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Camundongos , Camundongos Endogâmicos BALB C , Fator A de Crescimento do Endotélio Vascular/análiseRESUMO
Hemolymphangioma is a malformation of both lymphatic vessels and blood vessels. Splenic hemolymphangioma is extremely rare. Herein, we present a case of 62-year-old woman with ambiguous upper quadrant abdominal pain for two months who was found to have an occupying lesion in the spleen on computed tomography. She was eventually diagnosed with hemolymphangioma of the spleen. The patient underwent total splenectomy. Neither symptoms nor recurrence was found during the one-year follow-up period.
Assuntos
Linfangioma , Neoplasias Esplênicas , Dor Abdominal/etiologia , Biópsia , Feminino , Humanos , Linfangioma/complicações , Linfangioma/patologia , Linfangioma/cirurgia , Pessoa de Meia-Idade , Esplenectomia , Neoplasias Esplênicas/complicações , Neoplasias Esplênicas/patologia , Neoplasias Esplênicas/cirurgia , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Pancreatic lymphoepithelial cyst is a rare pancreatic lesion of undetermined pathogenesis, which is a true pancreatic cyst. Castleman's disease is a rare lymphoproliferative disorder, and a mesenteric location is unusual. The simultaneous occurrence of the two diseases are rarer than metachronous ones and has not been reported to date. We present a case report of a patient with simultaneous occurrence of pancreatic lymphoepithelial cyst and duodenal mesenteric Castleman's disease.