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Emodin, a natural anthraquinone derivative, can inhibit lipid synthesis and breast cancer cell proliferation. We previously found that emodin decreased breast cancer liver metastasis via epithelial-to-mesenchymal transition (EMT) inhibition. However, the mechanism through which emodin affects breast cancer liver metastasis in high-fat diet-induced obese and hyperlipidemic mice has not been elucidated. Bioinformatics analysis was used to reveal the potential targets and pathways of emodin. The mouse model of liver metastasis was established by injecting breast cancer cells into the left ventricle in high-fat diet-induced obese mice. The effect of emodin on inhibiting liver metastasis of breast cancer was evaluated by animal experiments. The mechanisms through which emodin inhibits liver metastasis of breast cancer were studied by cell and molecular biological methods. Emodin reduced lipid synthesis by inhibiting the expression of triglyceride (TG) synthesis-related genes, such as fatty acid synthase (Fasn), glycerol-3-phosphate acyltransferase 1 (Gpat1), and stearoyl-CoA desaturase (Scd1), and ultimately reduced liver metastasis in breast cancer. In addition, emodin inhibited breast cancer cell proliferation and invasion through the serine/threonine kinase (AKT) signaling and extracellular-regulated protein kinase (ERK) pathways by interacting with CSNK2A1, ESR1, ESR2, PIM1 and PTP4A3. Our results indicate that emodin may have therapeutic potential in the prevention or treatment of breast cancer liver metastasis.
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The high accumulation and poor penetration of nanocarriers in tumor is a contradiction of nanomedicine, which reduces the efficacy of chemotherapy. Due to the positive effect of hyperthermia on in vivo drug diffusion, we designed a magnetothermally sensitive micelle (MTM) by integrating magnetic targeting (MT), magnetic hyperthermia (MH), and magnetothermally responsive drug release to facilitate simultaneous drug accumulation and penetration in tumor. Accordingly, we synthesized a cyanine7-modified thermosensitive polymer with phase transition at 42.3°C, and utilized it to prepare drug-loaded MTMs by encapsulating superparamagnetic MnFe2O4 nanoparticles and doxorubicin (DOX). The obtained DOX-MTM had not only high contents of DOX (9.1%) and MnFe2O4 (38.7%), but also some advantages such as superparamagnetism, high saturation magnetization, excellent magnetocaloric effect, and magnetothermal-dependent drug release. Therefore, DOX-MTM improved in vitro DOX cytotoxicity by enhancing DOX endocytosis under the assistance of MH. Furthermore, MT and MH enhanced in vivo DOX-MTM accumulation and DOX penetration in tumor, respectively, substantially inhibiting tumor growth (84%) with excellent biosafety. These results indicate the development of an optimized drug delivery system with MH and MH-dependent drug release, introducing a feasible strategy to enhance the application of nanomedicines in tumor chemotherapy.
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Traditional Chinese tongue diagnosis plays an irreplaceable role in disease diagnosis. This study aimed to describe the tongue characteristics of patients with granulomatous lobular mastitis (GLM). Forty GLM patients and 40 non-GLM controls were evaluated using the Traditional Chinese Medicine subjective clinical interpretation and a TDA-1 Tongue Diagnostic and Analysis system. The associations between the image features of the tongue body and coating and the profiling of immune-inflammatory parameters were analyzed. GLM patients were prone to a reddish tongue bodies with thick, white, and greasy coatings. Thick and greasy tongue coating features are risk factors for GLM. GLM patients had higher levels of white blood cells (WBC), platelets, C-reactive protein, interleukin-2, and transforming growth factor-ß (TGF-ß) than non-GLM controls (Pâ <â .05). Also, tongue coating contrast and entropy values were significantly correlated with WBC or TGF-ß levels in GLM patients (râ <â -0.310 and Pâ <â .05). We demonstrated that the hot evil and phlegm-dampness constitutions are the main characteristics of GLM. This might provide a reference for GLM diagnosis.
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Mastitis Granulomatosa , Lengua , Humanos , Femenino , Mastitis Granulomatosa/diagnóstico , Medicina Tradicional China , Factor de Crecimiento Transformador betaRESUMEN
Background: The incidence and mortality of bladder cancer (BCa) are increasing, while the existing diagnostic methods have limitations. Therefore, for early detection and response prediction, it is crucial to improve the prognosis and treatment strategies. However, with existing diagnostic methods, detecting BCa in the early stage is challenging. Hence, novel biomarkers are urgently needed to improve early diagnosis and treatment efficiency. Methods: The gene expression profile and gene methylation profile dataset were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs), differentially methylated genes (DMGs), and methylation-regulated differentially expressed genes (MeDEGs) were gradually identified. A cancer genome map was obtained using online gene expression profile interaction analysis, and survival implications were produced using Kaplan-Meier survival analysis. GSEA was employed to predict the marker pathways where DEGs were significantly involved. The study used bisulfite PCR amplification combined with bisulfite amplicon sequencing (BSAS) to screen for methylation analysis of multiple candidate regions of the adenylate cyclase 2 (ADCY2) based on the sequence design of specific gene regions and CpG islands. Results: In this study, DEGs and DMGs with significantly up- or down-regulated expression were selected. The intersection method was used to screen the MeDEGs. The interaction network group in STRING was then visualized using Cytoscape, and the PPI network was constructed to identify the key genes. The key genes were then analyzed using functional enrichment. To compare the relationship between key genes and the prognosis of BCa patients, we further investigated ADCY2 and found that ADCY2 can be a potential clinical biomarker in BCa prognosis and immunotherapy response prediction. In human BCa 5637 and MGH1 cells, we developed and verified the effectiveness of ADCY2 primers using BSAS technology. The findings revealed that the expression of ADCY2 is highly regulated by the methylation of the promoter regions. Conclusion: This study revealed that increased expression of ADCY2 was significantly correlated with increased tumor heterogeneity, predicting worse survival and immunotherapy response in BCa patients.
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ETHNOPHARMACOLOGICAL RELEVANCE: Epimedium brevicornu Maxim. and Cullen corylifolium (L.) Medik. are part of a traditional Chinese medicine (TCM) drug pair (ECDP) widely used in the clinical treatment of breast cancer (BC). Both drugs have been proven to have anti-tumor effect. However, the active ingredients and molecular mechanism of ECDP remain to be explored. AIM OF THE STUDY: To explore the efficacy and potential mechanisms of actions of herb pair through network pharmacology and in vitro and in vivo experiments. MATERIALS AND METHODS: The active ingredients of ECDP were identified using high-performance liquid chromatography. The corresponding potential target genes for ECDP components and BC were extracted from established databases, and the protein-protein interaction network of shared genes was constructed using STRING database. The effective ingredients and targets of ECDP for BC were obtained through the TCMSP database and GeneCards database. The potential targets and pathways were selected through the protein interaction network and enrichment analysis. Proliferation and migration experiments in vitro and tumor growth in vivo were performed to evaluate the effects of Anhydroicaritin (AHI) on BC. RESULTS: AHI is the potential candidate active ingredient of ECDP through TCMSP. Molecular docking revealed that AHI has excellent binding ability with TP53, VEGFA, MMP2, and Met. In vitro experiment results showed that AHI inhibits the growth of MDA-MB-231, 4T1, MCF-7, and SK-BR-3 BC cells. The inhibitory effect of AHI on triple-negative BC cells is more obvious. With the increase of AHI concentration, the colony-forming, migration, and metastasis abilities of the MDA-MB-231 and 4T1 cells gradually decreases. In addition, Western blot and reverse transcription polymerase chain reaction analyses results indicated that AHI downregulates HIF-1α/VEGFA signaling in triple-negative BC cells. AHI inhibits tumor growth and lung metastasis while downregulating the expression of HIF-1α and VEGFA. CONCLUSION: AHI may play an anti-BC effect by inhibiting cancer cell proliferation, invasion, and metastasis. The results of this study may provide a theoretical basis for AHI research and the clinical application of ECDP in BC.
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Neoplasias de la Mama , Medicamentos Herbarios Chinos , Benzopiranos , Neoplasias de la Mama/tratamiento farmacológico , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Femenino , Humanos , Medicina Tradicional China , Simulación del Acoplamiento Molecular , Farmacología en RedRESUMEN
It was to investigate the role of Gegen Qinlian decoction (GQD) in the regulation of ABTB1 gene based on PI3K/AKT/FOXO1 signaling pathway in colorectal cancer (CRC) metastasis. In this study, 10 cases of the CRC mouse model were established by inoculating CT26 cells into the spleen of mice, which were divided into the experimental group and the control group, 5 cases in each group; the control group was intragastrically administered with normal saline 0.3 mL/d, and the experimental group was intragastrically administered with GQD 0.2 mL/d at a ratio of 0.2 g medicinal materials/10 g for 10 days and sacrificed, and pathological sections were made. The expression density of signaling pathway PI3K/AKT/FOXO1 as well as gene ABTB1 was detected in the sections of the two groups, and the mechanism of action of this gene in the two groups of mice was studied. It was found that the densities of p-PI3K, p-AKT, and p-FOXO1 in the experimental group of mice were 26.55 g/cm3, 70.2 g/cm3, and 24.36 g/cm3, respectively, which were significantly increased compared with the control group, P < 0.05; the density of ABTB1 was 35.4 g/cm3, which was significantly increased compared with the control group, P < 0.05; the proliferation and migration ability of CRC cells in the experimental group were significantly decreased, P < 0.05. GQD can promote the expression of ABTB1 by activating the PI3K/AKT/FOXO1 signaling pathway, in order to inhibit the proliferation and growth ability of CRC cells.
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Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Medicamentos Herbarios Chinos/farmacología , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Animales , Proliferación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Regulación hacia Abajo , Proteína Forkhead Box O1/metabolismo , Ratones , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de SeñalRESUMEN
Clear cell renal cell carcinoma (ccRCC) is the most common malignant type of kidney cancer. The present study aims to explore the underlying mechanism and potential targets of the traditional Chinese medicine Bu-Shen-Jian-Pi-Fang (BSJPF) in the treatment of ccRCC based on network pharmacology. After obtaining the complete composition information for BSJPF from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, we analyzed its chemical composition and molecular targets and then established a pharmacological interaction network. Twenty-four significantly differentially expressed genes and nine pathways mainly related to tumor proliferation were identified and screened. Functional enrichment analysis indicated that the potential targets might be significantly involved in glycolysis and the HIF-1 signaling pathway. To further confirm the effect of BSJPF on ccRCC cell proliferation, a BALB/c xenograft mouse model was constructed. Potential targets involved in regulating glycolysis and the tumor immune microenvironment were evaluated using RT-qPCR. VEGF-A expression levels were markedly decreased, and heparin binding-EGF expression was increased in the BSJPF group. BSJPF also inhibited tumor proliferation by enhancing GLUT1- and LDHA-related glycolysis and the expression of the immune checkpoint molecules PD-L1 and CTLA-4, thereby altering the immune-rejection status of the tumor microenvironment. In summary, the present study demonstrated that the mechanism of BSJPF involves multiple targets and signaling pathways related to tumorigenesis and glycolysis metabolism in ccRCC. Our research provides a novel theoretical basis for the treatment of tumors with traditional Chinese medicine and new strategies for immunotherapy in ccRCC patients.
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Antineoplásicos Fitogénicos/farmacología , Carcinoma de Células Renales/tratamiento farmacológico , Proliferación Celular/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Glucólisis/efectos de los fármacos , Neoplasias Renales/tratamiento farmacológico , Farmacología en Red , Escape del Tumor/efectos de los fármacos , Animales , Carcinoma de Células Renales/inmunología , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/patología , Línea Celular Tumoral , Bases de Datos Genéticas , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , Humanos , Neoplasias Renales/inmunología , Neoplasias Renales/metabolismo , Neoplasias Renales/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Mapas de Interacción de Proteínas , Transducción de Señal , Carga Tumoral/efectos de los fármacos , Microambiente Tumoral/inmunología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Long non-coding RNA (lncRNA) is a new type of non-coding RNA that has an important regulatory influence on several human diseases, including cancer metastasis. HOX antisense intergenic RNA (HOTAIR), a newly discovered lncRNA, has an important effect on tumour proliferation, migration and metastasis. HOTAIR regulates cell proliferation, changes gene expression, and promotes tumour cell invasion and migration. However, its molecular mechanism of action remains unknown. The present review summarizes the molecular mechanism and role of HOTAIR in tumour invasion and metastasis, discusses the association between HOTAIR and tumour metastasis through different pathways, such as the transforming growth factor ß, Wnt/ß-catenin, PI3K/AKT/MAPK and vascular endothelial growth factor pathways, emphasizes the function of HOTAIR in human malignant tumour metastasis and provides a foundation for its application in the diagnosis, prognosis and medical treatment of various tumours.
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Background: Breast cancer (BC) is the leading cause of cancer-related deaths among women worldwide. The application of advanced technology has promoted accurate diagnosis and treatment of cancer. Anhydroicaritin (AHI) is a flavonoid with therapeutic potential in BC treatment. The current study aimed to determine AHI's mechanism in BC treatment via RNA sequencing, comprehensive bioinformatics analysis, and experimental verification. Methods: Network pharmacology and MTT (3-(4,5)-dimethylthiazolyl-3,5- diphenyltetrazolium bromide) experiments were conducted to first confirm AHI's anti-BC effect. RNA sequencing was performed to identify the genes affected by AHI. Differential expression analysis, survival analysis, gene set enrichment analysis, and immune infiltration analysis were performed via bioinformatics analysis. Western blot analysis, reverse transcription-polymerase chain reaction (RT-PCR) experiment, molecular docking, and drug affinity responsive target stability (DARTS) experiments were also performed to confirm AHI's direct effect on glutathione peroxidase 1 (GPX1) expression. Confocal immunofluorescence analysis was conducted to verify AHI's effect on the occurrence and development of epithelial-mesenchymal transition (EMT). Finally, BC nude mouse xenografts were established, and AHI's molecular mechanism on BC was explored. Results: Network pharmacology results demonstrated that AHI's therapeutic targets on BC were related to the proliferation, invasion, and metastasis of BC cells. AHI significantly inhibited the proliferation of 4T1 and MDA-MB-231 BC cells in the MTT experiments. RNA sequencing results showed that AHI upregulated the GPX1 expression in the 4T1 and MDA-MB-231 BC cells. Next, bioinformatics analysis revealed that GPX1 is less expressed in BC than in normal breast tissues. Patients with high GPX1 expression levels tended to have prolonged overall survival and disease-free survival than patients with low GPX1 expression levels in BC. Western blot and RT-PCR experiments revealed that AHI increased the protein and mRNA levels of GPX1. Molecular docking and DARTS experiments confirmed the direct binding combination between AHI and GPX1. After the evaluation of the EMT scores of 1,078 patients with BC, we found a potential anti-BC role of GPX1 possibly via suppression of the malignant EMT. The confocal immunofluorescence analysis showed that AHI increased E-cadherin expression levels and reduced vimentin expression levels in BC cells. Animal experiments showed that AHI significantly inhibited tumor growth. AHI also inhibited EMT by enhancing GPX1 and caspase3 cleavage, hence inhibiting EMT markers (i.e., N-cadherin and vimentin) and Ki-67. Conclusion: GPX1 plays a critical role in BC, which may be a biomarker for the prognosis. In addition, AHI suppressed EMT by increasing GPX1 expression, which may serve as a potential therapy for BC treatment.
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Clear cell renal cell carcinoma (ccRCC) is one of the most common cancers worldwide. Despite intense efforts to elucidate its pathogenesis, the molecular mechanisms and genetic characteristics of this cancer remain unknown. In this study, three expression profile data sets (GSE15641, GSE16441 and GSE66270) were integrated to identify candidate genes that could elucidate functional pathways in ccRCC. Expression data from 63 ccRCC tumors and 54 normal samples were pooled and analyzed. The GSE profiles shared 379 differentially expressed genes (DEGs), including 249 upregulated genes, and 130 downregulated genes. A protein-protein interaction network (PPI) was constructed and analyzed using STRING and Cytoscape. Functional and signaling pathways of the shared DEGs with significant p values were identified. Kaplan-Meier plots of integrated expression scores were used to analyze survival outcomes. These suggested that FN1, ICAM1, CXCR4, TYROBP, EGF, CAV1, CCND1 and PECAM1/CD31 were independent prognostic factors in ccRCC. Finally, to investigate early events in renal cancer, we screened for the hub genes CCND1 and PECAM1/CD31. In summary, integrated bioinformatics analysis identified candidate DEGs and pathways in ccRCC that could improve our understanding of the causes and underlying molecular events of ccRCC. These candidate genes and pathways could be therapeutic targets for ccRCC.
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Biomarcadores de Tumor/análisis , Carcinoma de Células Renales/genética , Ciclina D1/genética , Neoplasias Renales/genética , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/genética , Carcinoma de Células Renales/patología , Progresión de la Enfermedad , Perfilación de la Expresión Génica , Humanos , Neoplasias Renales/patología , Pronóstico , TranscriptomaRESUMEN
OBJECTIVES: This study was aimed to evaluate whether single nucleotide polymorphisms (SNPs) of TLR4 and common living habits of prostate hyperplasia (BPH) patients would affect the subjects' risk and prognosis. MATERIALS AND METHODS: We totally recruited 501 BPH patients and 964 healthy controls. The patients' international prostate symptom score (IPSS) and quality of life assessment (QoL) were designated as the prognostic indexes for BPH patients. Altogether 7 SNPs within TLR4 were selected, and the interactions among SNPs and living habits were explained with multi-factor dimensionality reduction (MDR) modeling. RESULTS: The mutant alleles of rs10983755 (G>A) and rs1927907 (G>A) tended to put on risk of BPH, yet the wide alleles of rs4986791 (C>T) and rs115336889 (G>C) were associated with incremental susceptibility to BPH (P<0.05). The rs10983755 (GA) and rs1927907 (GA) were suggested as the marker of non-aggressive BPH, whereas rs4986791 (TT) could symbolize aggressive BPH (P<0.05). The homozygotes of rs4986791 (TT) and rs115336889 (CC) could improve the IPSS change, and rs115336889 (CC) was also correlated with more obviously ameliorated Qol change (P<0.05). Finally, MDR modeling suggested that rs4986791 (TT) and rs115336889 (GG) shaped the genotyping combination featured by the lowest risk of BPH when smoking or drinking history was also evaluated. CONCLUSION: The SNPs situated within TLR4 were potent candidates for predicting risk and prognosis of BPH patients, and their interactions within environmental parameters also helped to develop effective strategies for preventing and treating BPH.
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Triple negative breast cancer (TNBC) has the lowest survival rate of the breast cancer subtypes owing to its aggressive and metastatic behavior. It has been reported that peritumoral adipose tissue contributes to the cell invasiveness and dissemination of TNBC. Emodin is an active anthraquinone derivative isolated from Rheum palmatum, with anticancer properties that have been reported to inhibit lung metastasis in a nude mouse xenograft model. In the present study, the effects of emodin on human TNBC cells and adipocytes were investigated in vivo and in vitro. The TNBC cell lines MDAMB231 and MDAMB453 were cocultured with human adipocytes and treated with either emodin or epirubicin. Cell proliferation was assessed by MTT assay and migration and invasion were examined using a wound healing assay and a Transwell assay. interleukin8, CCchemokine ligand 5 (CCL5) and insulinlike growth factor1 levels in the culture supernatants were detected by ELISA. The epithelialmesenchymal transition (EMT) or metastasis associated markers were determined by western blot analysis. Nude mice fed with a high fat and sugar diet were used investigate the in vivo effect of emodin. The results showed that emodin inhibited TNBC proliferation and invasion more efficiently than epirubicin when cocultured with adipocytes by downregulating the level of CCL5 in adipocyte supernatants; inhibiting the expression level of protein kinase B (AKT); and activating glycogen synthase kinase3i (GSK3) and ßcatenin. This led to the suppressed expression of EMT and invasionassociated markers, including vimentin, snail, matrix metalloproteinase (MMP)2 and MMP9, and upregulation of Ecadherin, contributing to the inhibition of invasion. The in vivo assay showed that emodin inhibited tumor growth, and suppressed the lung and liver metastasis of TNBC cells by decreasing the secretion of CCL5 in mice fed a high fat and sugar diet more efficiently when compared with epirubicin. In conclusion, emodin inhibited the secretion of CCL5 from adipocytes, inhibited the EMT of TNBC cells, and inhibited tumor growth and lung and liver metastasis, which indicated a novel role of emodin in preventing the metastasis of TNBC.
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Adipocitos/metabolismo , Quimiocina CCL5/antagonistas & inhibidores , Quimiocina CCL5/metabolismo , Emodina/farmacología , Transición Epitelial-Mesenquimal/efectos de los fármacos , Neoplasias de la Mama Triple Negativas/patología , Adipocitos/efectos de los fármacos , Adulto , Animales , Biomarcadores de Tumor/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Técnicas de Cocultivo , Epirrubicina/farmacología , Femenino , Humanos , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Invasividad Neoplásica , Metástasis de la Neoplasia , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: In vitro and in vivo studies have shown that Zuo Jin Wan (ZJW), a herbal formula of traditional Chinese medicine (TCM), possessed anticancer properties. However, the underlying mechanism for the action of ZJW remains unclear. Various subtypes of 5-Hydroxytryptamine receptor (5-HTR) have been shown to play a role in carcinogenesis and cancer metastasis. 5-HTR1D, among the subtypes, is highly expressed in colorectal cancer (CRC) cell lines and tissues. The present study aimed at investigating effect of ZJW extracts on the biological function of CRC cells, the expression of 5-HTR1D, and molecules of Wnt/ß-catenin signaling pathway. METHODS: In this study, the effect of ZJW extracts on 5-HTR1D expression and Wnt/ß-catenin signaling pathway were investigated and contrasted with GR127935 (GR), a known 5-HTR1D antagonist, using the CRC cell line SW403. The cells were respectively treated with GR127935 and different doses of ZJW extracts. Proliferation, apoptosis, migration, and invasion of SW403 cells were compared between ZJW and GR127935 treatments. The expression of 5-HTR1D and signaling molecules involved in the canonic Wnt/ß-catenin pathway were determined by Western blot analysis. RESULTS: After ZJW extracts treatment and GR127935 treatment, G1 arrest in cell cycle of SW403 was increased. Cell apoptosis was pronounced, and cell migration and invasion were suppressed. SW403 cells showed a dose-dependently decreased expression of 5-HTR1D, meanwhile, ß-catenin level was significantly decreased in nucleus of cells cultured with GR127935. Treatment of ZJW extracts dose-dependently resulted in decreased 5-HTR1D and a concomitant reduction in the Wnt/ß-catenin signal transduction, an effect indistinguishable from GR127935 treatment. CONCLUSION: The anticancer activity of ZJW extracts may be partially achieved through attenuation of the 5-HTR1D-Wnt/ß-catenin signaling pathway.
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Neoplasias Colorrectales/metabolismo , Medicamentos Herbarios Chinos/farmacología , Receptores de Serotonina/metabolismo , Antagonistas de la Serotonina/farmacología , Vía de Señalización Wnt/efectos de los fármacos , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Medicamentos Herbarios Chinos/química , Humanos , Receptores de Serotonina/genéticaRESUMEN
Overexpression of 5-hydroxytryptamine (5-HT) in human cancer contributes to tumor metastasis, but the role of 5-HT receptor family in cancer has not been thoroughly explored. Here, we report overexpression of 5-HT(1D) receptor (5-HT(1D)R) was associated with Wnt signaling pathway and advanced tumor stage. The underlying mechanism of 5-HT(1D)R-promoted tumor invasion was through its activation on the Axin1/ß-catenin/MMP-7 pathway. In an orthotopic colorectal cancer mouse model, we demonstrated that a 5-HT(1D)R antagonist (GR127935) effectively inhibited tumor metastasis through targeting Axin1. Furthermore, in intestinal epithelium cells, we observed that 5-HT(1D)R played an important role in cell invasion via Axin1/ß-catenin/MMP-7 pathway. Together, our findings reveal an essential role of the physiologic level of 5-HT(1D)R in pulmonary metastasis of colorectal cancer.
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Proteína Axina/metabolismo , Neoplasias Colorrectales/metabolismo , Metaloproteinasa 7 de la Matriz/metabolismo , Receptor de Serotonina 5-HT1D/metabolismo , beta Catenina/metabolismo , Animales , Proteína Axina/genética , Western Blotting , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Movimiento Celular/genética , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Células HCT116 , Células HT29 , Humanos , Inmunohistoquímica , Masculino , Metaloproteinasa 7 de la Matriz/genética , Ratones Desnudos , Persona de Mediana Edad , Metástasis de la Neoplasia , Oxadiazoles/farmacología , Piperazinas/farmacología , Receptor de Serotonina 5-HT1D/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Antagonistas de la Serotonina/farmacología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Carga Tumoral/efectos de los fármacos , Carga Tumoral/genética , Ensayos Antitumor por Modelo de Xenoinjerto , beta Catenina/genéticaRESUMEN
OBJECTIVE: To evaluate the clinical outcome of Ruanjian Xiaoying Decoction (RJXYD) on chronic lymphocytic thyroiditis. METHODS: Eighty patients with chronic lymphocytic thyroiditis were randomly divided into RJXYD-treated group (n=40) and control group (n=40). The patients in the RJXYD-treated group received treatment of RJXYD combined with levothyroxine while the others in the control group received treatment of levothyroxine and prednisone both for 16 weeks. The serum levels of thyroid hormones and the titres of serum antithyroglobulin antibody (anti-TG Ab) and antithyroid microsomal antibody (anti-TM Ab) were all examined before and after treatment. The total response rates of the two groups were evaluated after treatment of 16 weeks. RESULTS: The total response rate of the RJXYD-treated group was 92.5%, while that of the control group was 60.0% (P<0.01). The serum levels of free triiodothyronine (FT(3)) and free thyroxine (FT(4)) were obviously increased after treatment as compared with those before treatment in the two groups. The titres of serum anti-TG Ab and anti-TM Ab and the serum level of thyroid-stimulating hormone (TSH) were all obviously decreased after treatment as compared with those before treatment in the two groups. CONCLUSION: The RJXYD can shrink and soften the enlarged thyroid gland and thyroid nodules, improve the immune function of human body, alleviate the response to thyroid self-antigens and promote the recovery of thyroid function.