RESUMO
MicroRNAs (miRNAs) have recently emerged as an important new class of cellular regulators that control various cellular processes and are implicated in human diseases, including cancer. Here, we show that loss of let-7 function enhances lung tumor formation in vivo, strongly supporting the hypothesis that let-7 is a tumor suppressor. Moreover, we report that exogenous delivery of let-7 to established tumors in mouse models of non-small-cell lung cancer (NSCLC) significantly reduces the tumor burden. These results demonstrate the therapeutic potential of let-7 in NSCLC and point to miRNA replacement therapy as a promising approach in cancer treatment.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , MicroRNAs/genética , Ensaios Antitumorais Modelo de Xenoenxerto , Animais , Sequência de Bases , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Linhagem Celular Tumoral , Humanos , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , MicroRNAs/administração & dosagem , RNA Antissenso/administração & dosagem , RNA Antissenso/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Carga TumoralAssuntos
Metildopa/farmacologia , Prolactina/metabolismo , Animais , Desoxiepinefrina/farmacologia , Dopamina/farmacologia , Haloperidol/farmacologia , Técnicas In Vitro , Masculino , Metildopa/metabolismo , Nordefrin/farmacologia , Hipófise/efeitos dos fármacos , Hipófise/fisiologia , Prolactina/sangue , Ratos , Receptores Dopaminérgicos/metabolismo , Hormônio Liberador de Tireotropina/farmacologia , Fatores de TempoAssuntos
Carbidopa/farmacologia , Di-Hidroxifenilalanina/metabolismo , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Prolactina/sangue , Animais , Química Encefálica , Masculino , Eminência Mediana/fisiologia , Mudanças Depois da Morte , Piridoxina/farmacologia , Ratos , Fatores de TempoAssuntos
Carbidopa/farmacologia , Hidrazinas/farmacologia , Fosfato de Piridoxal/metabolismo , Piridoxina/farmacologia , Animais , Encéfalo/metabolismo , Dopa Descarboxilase/metabolismo , Dopamina/metabolismo , Hipotálamo/metabolismo , Levodopa/metabolismo , Fígado/metabolismo , Masculino , Músculos/metabolismo , RatosRESUMO
Female rats received an ip injection of L-dopa on the afternoon of proestrus. L-Dopa reduced serum prolactin concentrations within 1 h, whether administered just prior to, or during, the normal surge in serum hormone level. This inhibition lasted for 2-3 h, after which serum prolactin concentrations rose substantially. Pretreatment of proestrous rats with MK-486, a peripheral inhibitor of aromatic-L-amino acid decarboxylase, did not block the effect of L-dopa on serum prolactin levels. In fact, MK-486 pretreatment appeared to prolong the effectiveness of L-dopa. Pretreatment with RO4-4602 at a dose sufficient to block central decarboxylase activity, however, did prevent dopa from inhibiting the proestrous surge in serum prolactin. These data are consistent with a role for dopamine in the control of prolactin secretion and suggest that the mechanism of action of L-dopa apparently does not require peripheral decarboxylation.
