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We explored the effects of curcumin on the aberrant biological behaviors of prolactinoma cells and the downstream pathways through which curcumin exerts its antitumor effects. We used quantitative reverse transcription-polymerase chain reaction assays to measure miR-206 expression levels in peripheral blood samples from patients with prolactinoma before and after curcumin treatment. We also investigated the proliferation level, viability, and invasion ability of groups of cells treated with different concentrations of curcumin using 3-(4,5)-dimethylthiahiazo (-z-y1)-3-di-phenytetrazoliumromide (MTT) assays, cell cloning assays, and Transwell assays, respectively. Furthermore, we determined the levels of autophagy-related proteins and protein kinase B/mammalian target of the rapamycin (Akt/mTOR) signaling pathway-related proteins in each group of treated cells by western blot. Curcumin treatment upregulated miR-206 expression levels in the peripheral blood of patients with prolactinoma and in GH3 cells. Knockdown of miR-206 expression enhanced the proliferation and invasive ability of GH3 cells, while curcumin treatment effectively inhibited the aberrant biological behavior of GH3 cells enhanced by miR-206 knockdown. miR-206 knockdown also activated the Akt/mTOR signaling pathway and inhibited autophagy in GH3 cells, and these changes were effectively reversed by curcumin treatment. Thus, curcumin inhibited the Akt/mTOR signaling pathway and promoted cell autophagy by miR-206 upregulation, resulting in antitumor effects that inhibited prolactinoma cell proliferation and invasion.
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Antineoplásicos , Curcumina , MicroARNs , Neoplasias Hipofisarias , Prolactinoma , Curcumina/administración & dosificación , Prolactinoma/sangre , Prolactinoma/tratamiento farmacológico , Neoplasias Hipofisarias/sangre , Neoplasias Hipofisarias/tratamiento farmacológico , Autofagia/efectos de los fármacos , Regulación hacia Arriba , Regulación de la Expresión Génica , MicroARNs/sangre , MicroARNs/genética , Transducción de Señal , Antineoplásicos/administración & dosificación , Masculino , FemeninoRESUMEN
Metabolism reprogramming plays an important role in tumorigenesis and osteosarcoma metastasis. Sine oculis homeobox 4 (SIX4) is reported to be a key transcription factor that is involved in glycolysis reprogramming of cancer cells. However, the role of SIX4 in osteosarcoma progression remains unknown. The expression profile of SIX4 in OS was evaluated in surgery samples of osteosarcoma patients. Functional studies were performed in vitro and in vivo. We found that SIX4 is significantly overexpressed in osteosarcoma and related to the undesirable prognosis of osteosarcoma patients. SIX4 promotes progression of osteosarcoma via upregulating isocitrate dehydrogenase 1 (IDH1), which provides novel prognostic biomarkers and promising therapeutic targets for osteosarcoma patients.
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Osteosarcoma , Transactivadores , Humanos , Transactivadores/metabolismo , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Regulación de la Expresión Génica , Osteosarcoma/genética , Isocitrato Deshidrogenasa/genéticaRESUMEN
Background: This study aimed to investigate the role of protein disulfide isomerase A3 (PDIA3) in oral squamous cell carcinoma (OSCC) and evaluate its significance as a diagnostic and prognostic biomarker. Methods: Comprehensive bioinformatics analysis of the OSCC dataset from The Cancer Genome Atlas (TCGA) was performed. PDIA3 was depleted in CAL27 and SCC25 OSCC cells by transfection with PDIA3-specific siRNA oligos. The effects of PDIA3 downregulation on cell viability, apoptosis, and cell migration were evaluated using CCK8, ELISA, and wound healing assays, respectively. Results: The mRNA and protein expression of PDIA3 was significantly up-regulated in OSCC tissues compared to adjacent normal tissues. Knockdown of PDIA3 led to significantly decreased cell viability, increased apoptosis, and suppressed migratory ability in OSCC cells. The Kaplan-Meier survival curve showed that patients with higher PDIA3 expression levels had shorter survival than those with low PDIA3 levels. The receiver operating characteristic (ROC) curve indicated that PDIA3 had high sensitivity and accuracy for detecting OSCC (area under the curve (AUC): 0.917, CI: 0.879-0.955). Univariate and multivariate Cox regression analyses identified PDIA3 as an independent prognostic factor of OSCC. Furthermore, the depletion of PDIA3 inhibited AKT activity in OSCC cells. Gene set enrichment analysis (GSEA) indicated that PDIA3 is involved in various important biological functions and signaling pathways closely related to cancer development. Conclusion: PDIA3 plays an oncogenic role in OSCC and represents a good candidate as a diagnostic and prognostic biomarker for OSCC.
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The effect of the TGF-ß pathway-based pituitary tumor of rats on the GH3 cell line after intervention with different concentrations of troglitazone (TGZ) is explored. The CH3 cell line of 24 clean male SD rats with pituitary adenoma is selected. The cells are divided into a blank contrast set and an experimental set. The experimental set is divided into different TGZ concentration sets, including 1 × 10-3 TGZ set, 1 × 10-4 TGZ set, and 1 × 10-5 TGZ set. The cell proliferation is detected by the CCK-8 method, the protein expressions of CD147, TGF-ß1, and MMP-9 are detected by the western blot method, and the relative mRNA expressions of CD147, TGF-ß1, and MMP-9 are detected by the qRT-PCR method. The expression levels of CD147, TGF-ß1, and MMP-9 in CH3 cells of pituitary adenoma rats are notoriously lower, while the expression of CD147, TGF-31, and MMP-9 could be reduced by TGZ acting on the GH3 cell line. The specific mechanism of action of this effect on the invasive ability of GH3 cell lines is multifaceted, suggesting that peroxisome proliferator activator-receptor (PPAR-γ) agonists have good clinical application prospects in tumor therapy and can provide new targets and approaches for tumor drug therapy.
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Neoplasias Hipofisarias , Tiazolidinedionas , Animales , Línea Celular , Cromanos/farmacología , Masculino , Metaloproteinasa 9 de la Matriz , Neoplasias Hipofisarias/genética , Ratas , Ratas Sprague-Dawley , Tiazolidinedionas/farmacología , Factor de Crecimiento Transformador beta , Factor de Crecimiento Transformador beta1 , TroglitazonaRESUMEN
BACKGROUND: Teratoma is a common tumor, but rarely occurs in the parotid region. Only nine cases have been reported in the current literature. Although it is generally detected in infancy or childhood, it is commonly asymptomatic. Computed tomography (CT) and magnetic resonance imaging (MRI) have important roles in the diagnosis of teratoma. CASE SUMMARY: A 36-year-old man developed a lump located below the left auricular lobule 3 years ago. Physical examination revealed a nearly-circular tumor in the left parotid gland region with a defined border, firm texture, and significant movement. Calcification, fat, keratinized substances, and typical fat-liquid levels was observed on CT and MRI. A diagnosis of cystic teratoma of the parotid gland was established preoperatively and confirmed by postoperative pathology. Following surgery, the patient developed temporary facial paralysis. There was no recurrence of teratoma during the 15-mo follow-up period. CONCLUSION: When an asymptomatic mass in the parotid region is identified, parotid gland teratoma should be included in the differential diagnosis. Imaging examinations are helpful in the diagnosis.
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Protein tyrosine kinase 7 (PTK7) expression has been reported to be dysregulated and to regulate various cellular activities in numerous types of cancer. However, to the best of our knowledge, the status and role of PTK7 in oral squamous cell carcinoma (OSCC) remains largely unknown. The present study aimed to investigate the involvement of PTK7 in OSCC progression and to determine the potential underlying mechanisms of action. The expression levels of PTK7 and dishevelled segment polarity protein 3 (DVL3) in OSCC cell lines were analyzed using reverse transcription-quantitative PCR and western blotting. A co-immunoprecipitation assay was used to verify the binding association between PTK7 and DVL3. In addition, OSCC cells were transfected with a short hairpin RNA targeting PTK7 or pcDNA-DVL3 overexpression vectors. The effect of PTK7 on OSCC cell viability, proliferation, migration and invasion, and the underlying mechanisms, were investigated using Cell Counting Kit-8, colony formation, wound healing and Transwell assays, respectively. Western blotting was used to analyze the expression levels of proliferation- and migration-associated proteins. The results revealed that the expression levels of both PTK7 and DVL3 were significantly upregulated in OSCC cell lines. In addition, a binding association was identified between PTK7 and DVL3 in SCC-9 cells. The knockdown of PTK7 expression inhibited OSCC cell viability, proliferation, invasion and migration, while the overexpression of DVL3 reversed the inhibitory effects of PTK7-knockdown on OSCC cells. In conclusion, the results of the present study suggested that PTK7 may be a key regulator of OSCC proliferation, migration and invasion, and PTK7-knockdown may inhibit OSCC cell viability, proliferation, invasion and migration by downregulating DVL3 expression. Therefore, PTK7 and DVL3 may represent potential biomarkers for diagnosis and treatment, as well as promising drug targets for OSCC.
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One of the very reliable, attractive, and cheapest techniques for synthesizing nanofibers for biomedical applications is electrospinning. Here, we have created a novel nanofibrous composite coated Ti plate to mimic an Extra Cellular Matrix (ECM) of native bone in order to enhance the bone tissue regeneration. An electrospun fibrous composite was obtained by the combination of minerals (Zn, Mg, Si) substituted hydroxyapatite (MHAP)/Polyethylene Glycol (PEG)/Cissus quadrangularis (CQ) extract. Fibrous composite's functionality, phase characteristics, and morphology were evaluated by FT-IR, XRD, and SEM techniques, respectively. The average fiber diameter of MHAP/PVA had decreased from ~274 to ~255 nm after incorporating PEG polymer. That further increased from ~255 to ~275 nm after adding CQ extract. Besides the bioactivity in SBF solution, the degradable nature was confirmed by immersing the fibrous composite in Tris-HCL solution. The degradable studies evaluate that the composite was degraded depending on time, and it degrades about 9.42% after 7 days of immersion. Osteoblasts like MG-63 cells differentiation, proliferation, and calcium deposition were also determined. These results show that this new fibrous composite exhibits advanced osteoblasts properties. Thus, we concluded that this new fibrous scaffold coated Ti implant could act as a better implant to mimic ECM of bone structure and to improve osteogenesis during bone regeneration.