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Int J Mol Sci ; 22(16)2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34445327


The fight against cancer is one of the main challenges for medical research. Recently, nanotechnology has made significant progress, providing possibilities for developing innovative nanomaterials to overcome the common limitations of current therapies. In this context, silver nanoparticles (AgNPs) represent a promising nano-tool able to offer interesting applications for cancer research. Following this path, we combined the silver proprieties with Artemisia arborescens characteristics, producing novel nanoparticles called Artemisia-AgNPs. A "green" synthesis method was performed to produce Artemisia-AgNPs, using Artemisia arborescens extracts. This kind of photosynthesis is an eco-friendly, inexpensive, and fast approach. Moreover, the bioorganic molecules of plant extracts improved the biocompatibility and efficacy of Artemisia-AgNPs. The Artemisia-AgNPs were fully characterized and tested to compare their effects on various cancer cell lines, in particular HeLa and MCF-7. Artemisia-AgNPs treatment showed dose-dependent growth inhibition of cancer cells. Moreover, we evaluated their impact on the cell cycle, observing a G1 arrest mediated by Artemisia-AgNPs treatment. Using a clonogenic assay after treatment, we observed a complete lack of cell colonies, which demonstrated cell reproducibility death. To have a broader overview on gene expression impact, we performed RNA-sequencing, which demonstrated the potential of Artemisia-AgNPs as a suitable candidate tool in cancer research.

Antineoplásicos , Apoptose/efeitos dos fármacos , Artemisia/química , Nanopartículas Metálicas , Prata , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Apoptose/genética , Artemisia/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Ensaios de Seleção de Medicamentos Antitumorais , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Química Verde , Células HeLa , Humanos , Células MCF-7 , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Células PC-3 , Extratos Vegetais/química , Prata/química , Prata/uso terapêutico
Genet Test Mol Biomarkers ; 25(7): 504-514, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34280005


Objective: This study was designed to analyze the expression of CSNK1D in hepatocellular carcinoma (HCC) and investigate the relationship between the expression of CSNK1D and the prognosis of HCC patients. Methods: The CSNK1D and alpha-fetoprotein (AFP) expression levels in patients with HCC and their corresponding clinical data were downloaded from The Cancer Genome Atlas (TCGA) and sorted with a Perl program. CSNK1D and AFP expression differences in liver tissue and liver cancer were compared and analyzed, based on the online database human cancer metastasis database, the relationships between the expression levels of CSNK1D and AFP and the proliferation and metastases of HCC were explored. The immunohistochemical data obtained from the Human Protein Atlas Database further verified the differences in the expression levels of CSNK1D and AFP in liver tissues and liver cancer tissues. Through Kaplan-Meier survival analysis, the effects of CSNK1D and AFP expression levels on the prognosis of patients with HCC were investigated, and the influences of and patients' gender, age and grades of cancer cells, tumor size, the status of lymph node metastasis, distant metastasis, and tumor stage on the expression of CSNK1D were analyzed with R language. The influence of differential expressions of CSNK1D on survival time was compared and the prognostic factors influencing the survival of HCC patients were statistically explored by univariate analysis and multivariate analysis. The potential influencing mechanism of CSNK1D on the prognosis of HCC patients was explored by Gene Set Enrichment Analysis (GSEA) enrichment. Results: The expression level of CSNK1D and AFP in cancer foci was significantly higher than that in normal tissues, However, in the same patient, the expression levels of AFP in paracarcinoma tissues and cancer tissues showed no significant difference. The expression level of CSNK1D in HCC with distant metastases was higher than that in those without metastasis, but the expression level of AFP in metastatic HCC was lower than that in those HCC without metastases. In immunohistochemical tests, CSNK1D was moderately positive in normal liver tissues, slightly positive in normal bile duct tissues, and highly positive in HCC. AFP was slightly positive in normal liver tissues and negative in HCC, but it was not detected in normal intrahepatic bile duct tissue. Survival analysis results suggested that the higher expression level of CSNK1D corresponded to the shorter survival period, whereas the expression level of AFP showed no significant influence on survival time. The expression level of CSNK1D was not correlated with gender, age, the status of lymph node metastasis status, or distant metastasis of patients. The main factors influencing the expression level of CSNK1D included tumor size, cancer cell grade, and tumor stage. The expression levels of CSNK1D in T2 and T3 were higher than that in T1. The expression levels of CSNK1D in G3 and G4 were higher than that in G1. The expression levels of CSNK1D in Stage II and Stage III were higher than that in Stage I. Univariate analysis suggested that tumor size, cell grade, distant metastasis, clinical stage, and CSNK1D expression level were the prognostic factors influencing the survival of patients. Multivariate analysis suggested that CSNK1D expression level was an independent factor influencing the prognosis of HCC patients. GSEA enrichment analysis indicated that CSNK1D mainly affected the prognosis of HCC patients through cell cycle, WNT signaling pathway, amino acid degradation metabolism, and other pathways. Conclusion: CSNK1D is an independent influencing factor for the prognosis of HCC patients and has the potential to be developed as a potential therapeutic target for HCC, and better than AFP in predicting the prognosis of HCC.

Carcinoma Hepatocelular/genética , Caseína Quinase Idelta/genética , Adulto , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/patologia , Caseína Quinase I/genética , Caseína Quinase I/metabolismo , Caseína Quinase Idelta/metabolismo , Bases de Dados Genéticas , Feminino , Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Estimativa de Kaplan-Meier , Fígado/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Transcriptoma/genética , alfa-Fetoproteínas/genética , alfa-Fetoproteínas/metabolismo