RESUMO
Patients received cranial-irradiation can be affected with cognitive deficits and decreasing hippocampal neurogenesis. In this work, we characterized the cognitive ability and immune-induced neurogenesis of the pre- and post-treated cranial-irradiated rats with Glatiramer acetate (GA), known as a weak CNS auto-antigen. The GA-treated rats displayed better cognitive abilities in Morris water maze (MWM). The numbers of Iba-I-positive microglia, BrdU(+)/DCX(+) cells and BrdU(+)/NeuN(+) cells in hippocampus increased, which are accompanied with increased IFN-γ and decreased IL-6, IL-4. Furthermore, GA reverted the Th1/Th2 balance. GA treatment can reverse the cognitive deficits caused by cranial irradiation through a mechanism that likely involves immunomodulation.
Assuntos
Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/etiologia , Irradiação Craniana/efeitos adversos , Hipocampo/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Transtornos Cognitivos/patologia , Citocinas/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta à Radiação , Proteína Duplacortina , Regulação da Expressão Gênica/efeitos dos fármacos , Acetato de Glatiramer , Hipocampo/patologia , Hipocampo/efeitos da radiação , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Proteínas dos Microfilamentos/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: The failure of hormone treatment for advanced prostate cancer might be related to aberrant activation of the androgen receptor. We have shown that (125)I labeled triple-helix forming oligonucleotide (TFO) against the androgen receptor gene inhibits androgen receptor expression and cell proliferation of LNCaP prostate cancer cells in vitro. This study aimed at exploring the effects of the (125)I-TFO on prostate tumor growth in vivo using a nude mouse xenograft model. METHODS: TFO was labeled with (125)I by the iodogen method. Thirty-two nude mice bearing LNCaP xenograft tumors were randomized into 4 groups and were intratumorally injected with (125)I-TFO, unlabeled TFO, Na(125)I and normal saline. Tumor size was measured weekly. The tumor growth inhibition rate (RI) was calculated by measurement of tumor weight. The expression of the androgen receptor gene was performed by RT-PCR and immunohistochemical study. The prostate specific antigen (PSA) serum levels were measured by enzyme linked immunosorbent assay. The tumor cell apoptosis index (AI) was detected by TUNEL assay. RESULTS: Tumor measurements showed that tumor development was significantly inhibited by either (125)I-TFO or TFO, with tumor RIs of 50.79% and 32.80% respectively. (125)I-TFO caused greater inhibition of androgen receptor expression and higher AIs in tumor tissue than TFO. Both the tumor weight and the PSA serum levels in (125)I-TFO treated mice ((0.93 +/- 0.15) g and (17.43 +/- 1.85) ng/ml, respectively) were significantly lower than those ((1.27 +/- 0.21) g and (28.25 +/- 3.41) ng/ml, respectively) in TFO treated mice (all P < 0.05). Na(125)I did not significantly affect tumor growth and androgen receptor expression in tumor tissue. CONCLUSIONS: The (125)I-TFO can effectively inhibit androgen receptor expression and tumor growth of human prostate cancer xenografts in vivo. The inhibitory efficacy of (125)I-TFO is more potent than that of TFO, providing a reference for future studies of antigen radiotherapy.