RESUMO
Bladder cancer is one of the most malignant tumors closely associated with macrophage immune dysfunction. The Chinese medicine polyporus has shown excellent efficacy in treating bladder cancer, with minimal side effects. However, its material basis and mechanism of action remain unclear. A new water-soluble polysaccharide (HPP) with strong immunomodulatory activity was isolated from the fungus Polyporus umbellatus (Pers.) Fries. HPP had an average molecular weight of 6.88 kDa and was composed mainly of an <-(1 â 4)-linked D-galactan backbone. The immunomodulatory activity of HPP was determined in vitro, and the results revealed that it could obviously increase the secretion of immune factors by IFN-γ-stimulated macrophages, including nitric oxide (NO), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), RANTES and interleukin-23 (IL-23), and the expression of the cell membrane molecule CD80. In addition, HPP was recognized by Toll-like receptor 2 (TLR2) and activated the signaling pathways of NF-κB and NLRP3 in a bladder cancer microenvironment model, indicating that HPP could enhance host immune system function. These findings demonstrated that HPP may be a potential immune modulator in the treatment of immunological diseases or bladder cancer therapy.
RESUMO
Bacillus CalmetteGuérin (BCG) is considered to be a successful biotherapy for treating bladder cancer (BCa). However, the underlying mechanisms of BCG have not been completely clarified, to date. The role of macrophages in BCG therapy for BCa has still not been determined in vivo. In the present study, the role and potential mechanism of BCG (0.25, 1.25 and 6.25 µg/mouse; intravenous) immunotherapy for BCa was investigated in a NOD/scid IL2Rg/ (NSI) mouse model by targeting macrophages in vivo. Notably, it was observed that NSI mice with T24 BCa cells displayed high levels of the macrophage marker CD11b+ F4/80+ after injection via the tail vein of live BCG, as well as a significant reduction in tumor volume. The levels of the inflammatory and macrophage maturation cytokines, such as tumor necrosis factorα, interleukin (IL)1ß, IL6, IL12P70, TNF superfamily member 11 and monocyte chemotactic protein 1, were significantly increased in the serum and the tumor supernatant compared to that in normal control subjects. Furthermore, BCG promoted the expression of the prodifferential genes Spi1 protooncogene, early growth response protein 1, nuclear factor (NF)κB and protooncogene cFos in bone marrow. In conclusion, these observations indicate that the injection of live BCG can target macrophages against bladder tumor growth in vivo. The mechanism is likely related to the promotion of macrophage maturation, immune activation and increased numbers of macrophages infiltrating the bladder tumor.
Assuntos
Adjuvantes Imunológicos/uso terapêutico , Vacina BCG/uso terapêutico , Macrófagos/imunologia , Neoplasias da Bexiga Urinária/terapia , Adjuvantes Imunológicos/farmacologia , Animais , Vacina BCG/imunologia , Linhagem Celular Tumoral , Citocinas/análise , Citocinas/imunologia , Modelos Animais de Doenças , Deleção de Genes , Humanos , Imunoterapia , Subunidade gama Comum de Receptores de Interleucina/genética , Ativação de Macrófagos , Masculino , Camundongos Endogâmicos NOD , Camundongos SCID , Mycobacterium bovis/imunologia , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/imunologiaRESUMO
Bladder cancer is one of the most malignant tumors closely associated with macrophages. Polyporus polysaccharide (PPS) has shown excellent efficacy in treating bladder cancer with minimal side effects. However, the molecular mechanisms underlying the effects of PPS in inhibiting bladder cancer remain unclear. In this study, we used macrophages cultured alone or with T24 human bladder cancer cell culture supernatant as study models. We found that PPS enhanced the activities of IFN-γ-stimulated RAW 264.7 macrophages, as shown by the release of inducible nitric oxide synthase (INOS), secretion of tumor necrosis factor (TNF)-α and interleukin (IL)-6, phagocytosis activity, as well as expression of M1 phenotype indicators, such as CD40, CD284 and CD86. PPS acted upstream in activation cascade of nuclear factor (NF)-κB signaling pathways by interfering with IκB phosphorylation. In addition, PPS regulated NF-κB (P65) signaling by interfering with Toll-like receptor (TLR)-4, INOS and cyclooxygenase (COX)-2. Our results indicate that PPS activates macrophages through TLR4/NF-κB signaling pathways.
Assuntos
Antineoplásicos/farmacologia , Polissacarídeos Fúngicos/farmacologia , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , NF-kappa B/genética , Polyporus/química , Microambiente Tumoral/genética , Animais , Antígenos CD/genética , Antígenos CD/metabolismo , Antineoplásicos/isolamento & purificação , Linhagem Celular , Linhagem Celular Tumoral , Meios de Cultivo Condicionados/farmacologia , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Polissacarídeos Fúngicos/isolamento & purificação , Regulação da Expressão Gênica , Humanos , Interferon gama/farmacologia , Interleucina-6/genética , Interleucina-6/metabolismo , Macrófagos/citologia , Macrófagos/metabolismo , Camundongos , Modelos Biológicos , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Transdução de Sinais , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Bexiga Urinária/metabolismo , Bexiga Urinária/patologiaRESUMO
OBJECTIVE: To establish a scientific method for identitication and evaluation of the Tibetan prescription Jia Ga Song Tang. METHODS: Volatile oil was extracted by water steam distillation and analyzed by GC-MS. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) were applied to the samples for chemical fingerprint pattern recognition research. RESULTS: 16 samples according to hierarchical cluster analysis (HCA) and principal component analysis (PCA) were divided into two classes, and results from two recognition analysis methods had good consistency. CONCLUSION: GC-MS-pattern recognition method was a kind of scientific, accurate and effective method for the quality evaluation of Jia Ga Song Tang.
Assuntos
Medicamentos de Ervas Chinesas/química , Cromatografia Gasosa-Espectrometria de Massas , Óleos Voláteis/química , Controle de Qualidade , Análise por Conglomerados , Medicamentos de Ervas Chinesas/normas , Óleos Voláteis/normas , Análise de Componente Principal , VaporRESUMO
OBJECTIVE: To analyze the chemical components of volatile components from Jia Ga Song Tang. METHODS: The volatile oils were extracted by water steam distillation. The chemical components of essential oil were analyzed by GC-MS and quantitatively determined by a normalization method. RESULTS: 103 components were separated and 87 components were identified in the volatile oil of Zingiberis Rhizoma. 58 components were separated and 38 components were identified in the volatile oil of Myristicae Semen. 49 components were separated and 38 components were identified in the volatile oil of Amomi Rotundus Fructus. 89 components were separated and 63 components were identified in the volatile oil of Jia Ga Song Tang. CONCLUSION: Eucalyptol, ß-phellandrene and other terpenes were the main compounds in the volatile oil of Jia Ga Song Tang. Changes in the kinds and content of volatile components can provide evidences for scientific and rational compatibility for Jia Ga Song Tang.
