RESUMO
Angiogenesis, the process of neovascularization, plays an important role in physiological and pathological conditions. ST104P is a soluble polysulfated-cyclo-tetrachromotropylene compound with anti-viral and anti-thrombotic activities. However, the functions of ST104P in angiogenesis have never been explored. In this study, we investigated the effects of ST104P in angiogenesis in vitro and in vivo. Application of ST104P potently suppressed the microvessels sprouting in aortic rings ex vivo. Furthermore, ST104P treatment significantly disrupted the vessels' development in transgenic zebrafish in vivo. Above all, repeated administration of ST104P resulted in delayed tumor growth and prolonged the life span of mice bearing Lewis lung carcinoma. Mechanistic studies revealed that ST104P potently inhibited the migration, tube formation and wound closure of human umbilical endothelial cells (HUVECs). Moreover, ST104P treatment inhibited the secretion and expression of matrix metalloproteinase-2 (MMP-2) in a dose-dependent manner. Together, these results suggest that ST104P is a potent angiogenesis inhibitor and may hold potential for treatment of diseases due to excessive angiogenesis including cancer.
Assuntos
Inibidores da Angiogênese/farmacologia , Endotélio Vascular/efeitos dos fármacos , Compostos Macrocíclicos/farmacologia , Metaloproteinase 2 da Matriz/biossíntese , Naftalenossulfonatos/farmacologia , Neovascularização Fisiológica/efeitos dos fármacos , Inibidores da Angiogênese/química , Inibidores da Angiogênese/uso terapêutico , Inibidores da Angiogênese/toxicidade , Animais , Animais Geneticamente Modificados , Aorta , Carcinoma Pulmonar de Lewis/irrigação sanguínea , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Movimento Celular/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Embrião não Mamífero/irrigação sanguínea , Embrião não Mamífero/efeitos dos fármacos , Endotélio Vascular/enzimologia , Endotélio Vascular/metabolismo , Indução Enzimática/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Compostos Macrocíclicos/química , Compostos Macrocíclicos/uso terapêutico , Compostos Macrocíclicos/toxicidade , Metaloproteinase 2 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Morfogênese/efeitos dos fármacos , Naftalenossulfonatos/química , Naftalenossulfonatos/uso terapêutico , Naftalenossulfonatos/toxicidade , Neovascularização Patológica/tratamento farmacológico , Peixe-Zebra/embriologiaRESUMO
Breast cancer is the most common cancer in women in the world and the second-most common cancer in women in Taiwan. However, breast cancer with plentiful leukemia blast-like cells circulating in the peripheral blood is very rare. A 48-year-old woman with breast cancer and leukemia-like manifestations was admitted in August, 2006. Special staining and immunophenotyping studies to determine the origin of her peripheral blast cells confirmed that they were from her breast carcinoma. Carcinocythemia (carcinoma cell leukemia) was diagnosed and then systemic chemotherapy and hormone therapy were given. Nevertheless, she expired 9 months after carcinocythemia presentation. The differential diagnosis of this condition, which is complicated by chemotherapy or radiotherapy for solid tumors, is very important. Patients with carcinocythemia have poor prognosis and survival.
