RESUMO
Previously, we designed a DNAzyme (beta1DE) targeting the human beta1 integrin subunit, which efficiently digested the mRNA of the beta1 integrin subunit and downregulated beta1 integrin expression in endothelial cells. This DNAzyme blocked the adhesion of endothelial cells and abolished their ability to form microcapillary tubes in Matrigel. In our present study, we demonstrate that beta1DE effectively inhibited neovascularization in Matrigel plugs (BALB/c mice, n=20) and solid human carcinoma tumors developed in nude mice (BALB/cA nude (nu-/-)-B6.Cg-Foxn1(nu)) (n=30) using prostate carcinoma cells PC-3 (n=15) and colon adenocarcinoma cells CX1.1 (n=15). When injected intratumorally, it significantly reduced the tumor size and number of microvessels developed by both CX1.1 and PC-3 cells within the 3 weeks of experiment duration. Thus, DNAzymes targeting beta1 integrin genes can inhibit multiple key tumorigenic processes in vitro and in vivo and may serve as useful anti-cancer agents.
Assuntos
Neoplasias do Colo/genética , DNA Catalítico/metabolismo , Integrina beta1/genética , Neovascularização Patológica/genética , Neoplasias da Próstata/genética , RNA Mensageiro/genética , Animais , Linhagem Celular Tumoral , Neoplasias do Colo/irrigação sanguínea , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , DNA Catalítico/genética , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Terapia Genética , Humanos , Integrina beta1/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neovascularização Patológica/metabolismo , Neoplasias da Próstata/irrigação sanguínea , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
PURPOSE: Lymph nodes estimated as pNO in conventional morphological studies could have focuses of carcinoma cells with a diameter of < or =2 mm referred to as micrometastases (pN+). Matrix metalloproteinases (MMPs) are proteolytic family of endopeptidases which are capable to degrading components of the extracellular matrix and play an important role in cancer invasion and metastases. The aim of this study was to investigate MT1-MMP expression in carcinoma of the larynx and analyze morphological parameters to relate the expression to CKs in pN0 lymph nodes. MATERIAL AND METHODS: To presented the direct correlation between 6 morphological features of tumor front and the probability of micrometastases and prediction of prognosis 22 patients operated for squamous cell carcinoma of the larynx were analyzed. The total score of TFG, chosen clinicomorphological features and grade of matrix metalloproteinase membrane type 1 staining in tumor front were analyzed to predict the presence of micrometastases and prognosis. Immunohistochemical methods with a panel of CKs antigens in lymph nodes and MT1-MMP expression in tumor tissue were per-lymph nodes. There was no significant relationship for immunoexpression of MT1-MMP and positive poliCKs stain. CONCLUSIONS: The results of study suggest that extended traditional pathologic evaluation by features from the TFG classification could aid in diagnosis of micrometastases. The positive expression of poliCKs in the pN0 lymph nodes appears to play an important role in determining prognosis in patients with carcinoma of the larynx.
