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1.
J Colloid Interface Sci ; 605: 752-765, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34365311

RESUMO

One major challenge of photothermal therapy (PTT) is achieving thermal ablation of the tumor without damaging the normal cells and tissues. Here, we designed a self-regulating photothermal conversion system for selective thermotherapy based on self-assembling gold nanoparticles (S-AuNPs) and investigated the selectivity effect using a novel home-made in vitro selective photothermal transformation model and an in vivo skin damaging assessment model. In the in vitro selective photothermal transformation model, laser irradiation selectively increased the temperature of the internal microenvironment (pH 5.5) and resulted in an obvious temperature difference (ΔT ≥ 5 °C) with that of the external environment (pH 7.4). More importantly, in the in vivo skin damaging assessment model, S-AuNPs achieved good tumor inhibition without damaging the normal skin tissue compared with the conventional photothermal material. This work provides not only a novel validation protocol for tumor thermotherapy to achieve the biosafety of specifically killing tumor cells and normal tissue but also an evaluation methodology for other precise therapy for cancers.


Assuntos
Hipertermia Induzida , Nanopartículas Metálicas , Nanopartículas , Neoplasias , Linhagem Celular Tumoral , Ouro , Humanos , Neoplasias/terapia , Fototerapia , Microambiente Tumoral
2.
J Colloid Interface Sci ; 605: 851-862, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34371428

RESUMO

Photodynamic therapy (PDT) of tumor has achieved good results, but the treatment efficiency is not high due to the lack of effective photosensitizers and tumor hypoxia. In this study, iridium dioxide nanoparticles (IrO2 NPs) with excellent photothermal/photodynamic effects and catalase like activity were synthesized by a simple method. The combination of glucose oxidase (GOx) and IrO2 NPs is formed by hyaluronic acid (HA), which have the activities of glucose oxidase and catalase, can target tumor sites and form in situ amplifiers in tumor microenvironment (IrO2-GOx@HA NPs). Firstly, GOx convert the high levels of glucose in the tumor to hydrogen peroxide (H2O2), and then IrO2 NPs convert H2O2 to oxygen (O2), which can enhance the type II of PDT. IrO2 NPs also can be used as a thermosensitive agent for photothermal therapy (PTT). In cancer cells, IrO2-GOx@HA NPs-mediated amplifier enhances the effect of type II of PDT, aggravating the apoptosis of breast cancer (4T1) cells and cooperating with its own PTT to further improve the overall treatment effect. Under simulated hypoxic conditions of tumor tissue, it was found that IrO2-GOx@HA NPs treatment can effectively relieve hypoxia inside tumor tissue. In addition, the results in vivo further proved that, IrO2-GOx@HA NPs can enhance the role of II PDT and cooperate with PTT to treat breast cancer effectively. The results highlight the prospect of IrO2-GOx@HA NPs in controlling and regulating tumor hypoxia to overcome the limitations of current cancer therapy.


Assuntos
Neoplasias da Mama , Nanopartículas , Neoplasias , Fotoquimioterapia , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Feminino , Humanos , Peróxido de Hidrogênio , Irídio , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Terapia Fototérmica , Microambiente Tumoral
3.
Gene ; 806: 145922, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34454032

RESUMO

Gastric cancer (GC)-derived cell lines were generally used in basic cancer research and drug screening. However, it is always concerned about the difference between cultured cells and primary tumor by oncologists. To address this question, we compared differentially expressed genes (DEGs) in primary cancers, healthy tissues, and cell lines both in vitro and in silico. Seven reported genes with decreased expression in GCs by DNA methylation were analyzed in our cohort studies and experimentally validation. Selected datasets from TCGA (The Cancer Genome Atlas), CCLE (The Broad Institute Cancer Cell Line Encyclopedia), and GTEx (The Genotype-Tissue Expression project) were used to represent GCs, GC-derived cell lines, and healthy tissues respectively in the in silico analysis. Thirty gastric tissues together with six cell lines were used for validations. Unexpectedly, we experimentally found that reported cancer-related downregulated genes were only found in cancer cell lines but not in biopsies. The unchanged gene expressions in primary GCs were generally consistent with our cohort study, using information from cancerous (TCGA) and healthy tissues (GETx). Substantial differences were also found between DEGs of cancer tissues (TGCA)/ healthy tissues (GTEx) pair and cell lines (CCLE)/ healthy tissues (GTEx) pair, which confirmed the significant differences between primary cancer and cancer cell lines. Moreover, elevated expression of YWHAQ (14-3-3 δ) and THBS1 were observed in the GC biopsies, which might be potential biomarkers for GC diagnosis, considering the increased YWHAQ and THBS1 associated with poor survival rates in gastric cancer patients. In sum, it is suggested that cautions should be taken when using GC cell lines to study genes that show great differences between cell lines and tissues.


Assuntos
Proteínas 14-3-3/genética , Regulação Neoplásica da Expressão Gênica , Proteínas de Neoplasias/genética , Neoplasias Gástricas/genética , Trombospondinas/genética , Proteínas 14-3-3/metabolismo , Idoso , Atlas como Assunto , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Metilação de DNA , Conjuntos de Dados como Assunto , Epigênese Genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Proteínas de Neoplasias/metabolismo , Cultura Primária de Células , Prognóstico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Análise de Sobrevida , Trombospondinas/metabolismo , Células Tumorais Cultivadas
4.
J Colloid Interface Sci ; 606(Pt 2): 1219-1228, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492460

RESUMO

To minimize unwanted reactions with high concentrations of reduced glutathione (GSH) in the tumor microenvironment (TME) during chemodynamic therapy (CDT), a simple and effective strategy was developed to fabricate a TME stimuli-responsive theranostic nanomedicine (Fe-CD) for fluorescence imaging-guided GSH depletion and cancer therapy by combining fluorescent imaging carbon dots (CD) and Fe(III). Introducing Fe(III) into Fe-CD not only quenched the fluorescence of CD while reacting with and consuming intracellular GSH for fluorescence imaging of the depletion of GSH but also provided a source of metal ions to generate more abundant hydroxyl radicals (•OH) with hydrogen peroxide (H2O2) through the Fenton reaction to improve CDT. Fe-CD showed promising •OH generation under H2O2 to effectively degrade methylene blue in vitro and obviously activate the green fluorescence of the reactive oxygen species (ROS) probe in cells. Benefiting from the fluorescence enhancement in response to TME stimulation, Fe-CD greatly enhanced CDT cytotoxicity while monitoring successful GSH depletion by fluorescence imaging. Fe-CD has the potential to act as a theranostic nanomedicine for fluorescence imaging-guided GSH depletion to amplify CDT.


Assuntos
Nanopartículas , Neoplasias , Pontos Quânticos , Carbono , Linhagem Celular Tumoral , Compostos Férricos , Glutationa , Humanos , Peróxido de Hidrogênio , Imagem Óptica , Nanomedicina Teranóstica , Microambiente Tumoral
5.
J Colloid Interface Sci ; 606(Pt 2): 1488-1508, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34500153

RESUMO

The combination of chemotherapy (CT) and chemodynamic therapy (CDT) is an emerging therapeutic strategy for tumors; however, its therapeutic efficacy is usually impaired by the shortage of high-efficiency intracellular catalysts for CDT and the poor tumor selectivity of CT. To address this concern, novel carrier-free nanodrugs (CMC-DD2) self-assembled from the natural melanin complex (CMC) with a superior CDT performance, and dehydroabietic acid hexamer (DD2) displaying a potent antitumor activity were proposed for the synergistic combination of CT and CDT. CMC-DD2 preferred to enter tumor cells and localize in the nucleus after lysosome escape due to its pH-dependent charge-reversal properties. Nanodrugs internalized by the nucleus directly bound the DNA and altered its conformation. Then, the dissociation of CMC-DD2 was efficiently triggered by intracellular hydrogen peroxide (H2O2) with the release of DNA damaging agents, including nitrate anions, hydroxyl radicals (●OH) and DD2. Finally, severe DNA damage induced mitochondrial apoptosis in HepG2 cells. An in vivo assessment further demonstrated the superior tumor selectivity and suppressor capacity and no/low toxicity of the nanodrugs. Overall, novel carrier-free, charge-reversal, nucleus-targeting, biodegradable, and DNA-affinity nanodrugs represent safe and effective platforms for the combination of CT and CDT.


Assuntos
Nanopartículas , Neoplasias , Linhagem Celular Tumoral , DNA , Células Hep G2 , Humanos , Peróxido de Hidrogênio , Radical Hidroxila , Neoplasias/tratamento farmacológico
6.
Talanta ; 237: 122952, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34736678

RESUMO

Development of noninvasive bioimaging fluorescent probes for detecting particular enzyme activity is greatly recommendable for preclinical diagnosis of cancer. Given that the elevated ß-gal activity is positively correlated with several tumors, developing a fluorescent probe for the sensing of ß-gal is therefore highly desirable for cancer diagnosis. Herein, a new enzyme-activatable near-infrared (NIR) turn-on fluorescent probe (DMC-ßgal) was developed for accurately detecting ß-gal activity characterized by excellent selectivity, high sensitivity (LOD = 0.298 U/L), and low toxicity. More importantly, DMC-ßgal qualifies remarkable NIR excitation (725 nm) and emission wavelength (770 nm), an ideal tool for restrained photodamage and suppressed autofluorescence. The above excellent performance of DMC-ß-gal allowed for the accurate monitoring of endogenous ß-gal in living cells. Moreover, the probe was successfully applied to detect intracellular ß-gal activity in different types of cancer cells, verifying that SKOV-3 cells had a higher level of ß-gal activity than those of A549, HCT-116, MCF-7, and HepG2 cells. Furthermore, DMC-ßgal could real-time visualize endogenously ß-gal in tumor-bearing nude mice with low auto-fluorescence interference. All results fully demonstrated that DMC-ßgal has potential value as a promising strategy for diagnosis of ß-gal-related diseases.


Assuntos
Corantes Fluorescentes , Imagem Óptica , Animais , Linhagem Celular Tumoral , Camundongos , Camundongos Nus , beta-Galactosidase
7.
J Colloid Interface Sci ; 607(Pt 1): 34-44, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34492351

RESUMO

Among the strategies to fight cancer, multi-therapeutic approaches are considered as a wise choice to put in place multiple weapons to suppress tumors. In this work, to combine chemotherapeutic effects to magnetic hyperthermia when using biocompatible scaffolds, we have established an electrospinning method to produce nanofibers of polycaprolactone loaded with magnetic nanoparticles as heat mediators to be selectively activated under alternating magnetic field and doxorubicin as a chemotherapeutic drug. Production of the fibers was investigated with iron oxide nanoparticles of peculiar cubic shape (at 15 and 23 nm in cube edges) as they provide benchmark heat performance under clinical magnetic hyperthermia conditions. With 23 nm nanocubes when included into the fibers, an arrangement in chains was obtained. This linear configuration of magnetic nanoparticles resemble that of the magnetosomes, produced by magnetotactic bacteria, and our magnetic fibers exhibited remarkable heating effects as the magnetosomes. Magnetic fiber scaffolds showed excellent biocompatibility on fibroblast cells when missing the chemotherapeutic agent and when not exposed to magnetic hyperthermia as shown by viability assays. On the contrary, the fibers containing both magnetic nanocubes and doxorubicin showed significant cytotoxic effects on cervical cancer cells following the exposure to magnetic hyperthermia. Notably, these tests were conducted at magnetic hyperthermia field conditions of clinical use. As here shown, on the doxorubicin sensitive cervical cancer cells, the combination of heat damage by magnetic hyperthermia with enhanced diffusion of doxorubicin at therapeutic temperature are responsible for a more effective oncotherapy.


Assuntos
Hipertermia Induzida , Nanopartículas de Magnetita , Neoplasias , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Compostos Férricos , Campos Magnéticos , Poliésteres
8.
J Colloid Interface Sci ; 607(Pt 1): 1-15, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34500412

RESUMO

The intracellular O2-supply not only can relieve tumor hypoxia but also enhance the effects of photodynamic therapy (PDT). In this work, metallic Mo2C@N-carbon@PEG nanoparticles were constructed to reveal the near infrared (NIR)-photocatalytic O2 generation and promote photodynamic therapy (PDT). Here, (NH4)6Mo7O24·4H2O nanorods and urea were adopted as resources that were calcined to obtain Mo2C@N-carbon nanoparticles (20 nm). All samples displayed high NIR absorption as well as photothermal conversion efficiency of up to 52.7 % (Mo2C@N-Carbon-3@PEG). The density functional theory calculations demonstrated the metallic characteristic of Mo2C and that the consecutive interband/intraband charge-transition was responsible for the high NIR harvest and redox ability of electron-hole pairs, making the NIR-photocatalytic O2 and reactive oxygen species (ROS) generation. In comparison with the pure Mo2C, the heterostructure displayed twice the performance due to the enhanced charge-segregation between Mo2C and N-carbon. Given the high X-ray absorption coefficient and photothermal ability, the nanocomposite could be used in novel computer tomography and photothermal imaging contrast. Furthermore, the novel biodegradation and metabolism behaviors of nanocomposites were investigated, which were reflected as elimination from the body (mouse) via feces and urine within 14 days. The as-synthesized Mo2C@N-Carbon@PEG nanocomposites integrated the dual-model imaging, intracellular O2-supply, and phototherapy into one nanoplatform, revealing its potential for anti-cancer therapy.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Animais , Carbono , Linhagem Celular Tumoral , Camundongos , Molibdênio , Neoplasias/tratamento farmacológico , Oxigênio , Fototerapia
9.
Gene ; 807: 145964, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34530087

RESUMO

AIMS: We aimed to investigate the role of G protein subunit alpha Z(GNAZ) in the progression and prognosis of patients with hepatocellular carcinoma (HCC). METHODS: Oncomine, GEO, TCGA, GEPIA2, Kaplan-Meier Plotter, TIMER2, Metascape, CCLE, LinkedOmics, and UALCAN databases were used to analyze the differential expression of GNAZ in HCC and normal liver tissues, relationship between GNAZ expression and prognosis of patients with HCC, and expression of GNAZ in common human HCC cell lines. Western blotting was performed to analyze GNAZ expression, while the Cell Counting Kit 8 assay was used to determine cell proliferation, and flow cytometry was used to evaluate the cell cycle and apoptosis. Wound healing and transwell invasion assays were used to investigate cell metastasis and invasion. RESULTS: Using Oncomine, Gene Expression Omnibus (GEO), and GEPIA2 databases, GNAZ was found to be overexpressed in HCC tissues compared with that in adjacent normal liver tissues, and western blotting analysis showed GNAZ overexpression in seven patients with HCC who underwent surgical resection of HCC and para-cancerous tissues (p < 0.01). Survival analysis revealed that high GNAZ expression was negatively associated with overall survival (OS), recurrence-free survival, progression-free survival, and disease-specific survival in patients with HCC (p < 0.05). GNAZ overexpression was associated with worse 4- month, 6- month, 12- month, 24- month, 36- month, 48- month, and 60-month OS, as well as with different clinicopathological characteristics of patients with HCC, including hepatitis virus infection state; alcohol consumption state; male; female; Asian; microvascular invasion, Stage I-II, Stage II-III, and Stage III-IV; and grade II (Cox regression, p < 0.05). KEGG/GO biological process enrichment indicated that the genes similar to GNAZ in HCC were mainly enriched in the cell cycle, cell cycle phase transition, DNA replication checkpoint, and regulation of G0 to G1 transition. siRNA-GNAZ significantly reduced the viability of JHH-2 and SNU-761 cells from 12 to 96 h; increased the percentage of cells in the G0/G1 phase and decreased that of cells in the S and G2/M phases (p < 0.05); and markedly downregulated the expression of cyclin D, cyclin E, and CDK2 protein. siRNA-GNAZ also significantly increased the percentage of JHH-2 and SNU-761 cell apoptosis at late stages, while the number of surviving cells decreased (p < 0.05), and upregulated the expression of apoptosis-related proteins Bax and caspase 3 protein. Furthermore, siRNA-GNAZ remarkably reduced the healing of scratch wounds in JHH-2 and SNU-761 cells and the number of invasive cells compared with that in the control group (p < 0.001). CONCLUSION: Our study demonstrated that GNAZ plays a pivotal role as a potential oncogene and predicts poor prognosis in patients with HCC. It promotes tumor proliferation via cell cycle arrest, apoptosis, migration, and invasion. Thus, GNAZ may be a potential candidate biomarker providing useful insight into hepatocarcinogenesis and aggressiveness.


Assuntos
Carcinoma Hepatocelular/genética , Pontos de Checagem da Fase G1 do Ciclo Celular/genética , Subunidades alfa de Proteínas de Ligação ao GTP/genética , Idoso , Apoptose/genética , Grupo com Ancestrais do Continente Asiático/genética , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/mortalidade , Ciclo Celular/genética , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , China , Feminino , Subunidades alfa de Proteínas de Ligação ao GTP/metabolismo , Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/genética , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Transcriptoma/genética
10.
J Colloid Interface Sci ; 605: 263-273, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34332405

RESUMO

Calcium based biomaterials were widely used for drug delivery application due to their biodegradability, biocompatibility, and high drug loading capacity. Herein, amino-capped polyamidoamine (PAMAM) dendrimer was applied as a macromolecular template to form amino-modified calcium phosphate hollow sphere (CaPO-NH2). After loading with 5-fluorouracil (5Fu), this system performed synergistic cancer chemotherapy. In this study, the 5Fu/CaPO-NH2 particles could be efficiently uptaken by cancer cells, and then decompose into Ca2+ and release 5Fu drug in the cytoplasm; therefore calcium overload and reactive oxygen species (ROS) accumulation were found in PSN1 cells that could induce cell membrane damage and elicit cell apoptosis through a series of biochemical reactions including endoplasmic reticulum stress, lipid peroxidation and mitochondrial apoptosis. In the PSN1 pancreatic cancer xenograft model, the 5Fu/CaPO-NH2 system performed high tumor inhibition via chemotherapy and calcium overload induced apoptosis. Comparingly, the normal cells and organs were insensitive to this synergistic therapy, which indicated the well biocompatibility of delivery system. Thus, this study provided a promising CaPO-NH2 drug delivery platform for enhanced 5Fu chemotherapeutic effect.


Assuntos
Fluoruracila , Neoplasias Pancreáticas , Apoptose , Fosfatos de Cálcio , Linhagem Celular Tumoral , Portadores de Fármacos , Fluoruracila/farmacologia , Humanos , Neoplasias Pancreáticas/tratamento farmacológico
11.
Spectrochim Acta A Mol Biomol Spectrosc ; 266: 120458, 2022 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-34619508

RESUMO

Near-infrared (NIR) photothermal therapy is an effective partner to the chemotherapy of tumors with the merits of high therapeutic ability and slight side effect on normal tissues. Herein, we synthesized gold nanorods and assembled them with L-cysteine reduced graphene oxide (AuNR@Lcyst-rGO) for efficient photothermal therapy. The high therapeutic efficacy of AuNR@Lcyst-rGO can be due to the high photothermal effect of gold nanorods and reduced graphene oxide, and the synergistic effect of them. The nontoxicity of L-cysteine also guarantees the comfortable biocompatibility of reduced graphene oxide, which is essential for the photothermal absorber used in human tissue. The results demonstrate that assembly of gold nanorods with reduced graphene oxide (AuNR@Lcyst-rGO) is a promising photothermal agent with high efficient NIR-triggered photothermal therapy efficiency, excellent stability, superior biocompatibility.


Assuntos
Grafite , Nanotubos , Neoplasias , Linhagem Celular Tumoral , Cisteína , Ouro , Humanos , Neoplasias/terapia , Fototerapia , Terapia Fototérmica
12.
Environ Pollut ; 292(Pt B): 118370, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34656677

RESUMO

Benzophenone-1 (BP-1) belongs to personal care product-related contaminants of emerging concern and has been recently reported to induce xenoestrogenic effects. However, the underlying mechanisms leading to the activation of target receptors and subsequent various adverse outcomes remain unclear, which is beneficial to safety and health risk assessment of benzophenone-type ultraviolet filters with their widespread occurrence. Herein, we investigated disrupting effects of BP-1 at environmentally relevant concentrations (10-9-10-6 M) on estrogen receptor (ER) α-associated signaling pathways. Molecular dynamics simulations together with yeast-based assays revealed the steady binding of BP-1 to ERα ligand binding domain (LBD) and hence the observed agonistic activity. BP-1 triggered interaction between ERα and ß-catenin in human SKOV3 ovarian cancer cells and caused translocation of ß-catenin from the cytoplasm to the nucleus, leading to aberrant activation of Wnt/ß-catenin. BP-1 consequently induced dissemination of SKOV3 via regulating epithelial-mesenchymal transitions (EMT) biomarkers including minimally downregulating ZO-1 gene to 78.0 ± 10.1% and maximally upregulating MMP9 gene to 144.1 ± 29.7% and promoted 1.03-1.83 fold proliferation, migration and invasion of SKOV3. We provide the first evidence that the BP-1 activated ERα triggers crosstalk between ERα and Wnt/ß-catenin pathway, leading to the abnormal stimulation and progression of SKOV3 cancer cells.


Assuntos
Neoplasias Ovarianas , Via de Sinalização Wnt , Benzofenonas/toxicidade , Linhagem Celular Tumoral , Proliferação de Células , Receptor alfa de Estrogênio , Feminino , Humanos
13.
Chemosphere ; 287(Pt 1): 131967, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34438215

RESUMO

Perfluorinated iodine alkanes (PFIs) can serve as an important raw materials for the synthesis of various perfluorinated chemical products through telomerization reaction. The estrogenic effects of PFIs have been reported previously by some in vitro and in vivo screening assays. To explore the potential epigenetic toxicity of PFIs, activation of lncRNAs was screened, and the cell motility changes induced by perfluorooctyl iodide (PFOI) were analyzed in this study. High metastatic bladder cell line (T24) was used to investigate the cellular migration function affected by PFOI. PFOI exposure significantly induced the upregulation of lncRNA anril, thorlnc, hotairm1, meg3, and malat1. The migration and invasion of T24 cells were also enhanced upon PFOI exposure. The transcription level of matrix metalloenzyme genes, epidermal growth factors, cytoskeleton genes, and the upstream factors involved in cell motility pathways were examined to illustrate possible mechanisms. Additionally, the basic role of malat1 in cellular motility was investigated by lncRNA knockdown and migration assays. The knockdown of malat1 inhibited the cellular motility induced by PFOI. The levels of MMP-2/-9 genes were also down-regulated by the treatment of si-malat1. Overall, the perturbation of cytoskeleton genes (E-cadherin/N-cadherin) may account for the impact on the motility of T24 cells. Our studies indicate that perfluorinated chemicals might regulate the lncRNAs, thus promoting the metastasis of the tumor cells.


Assuntos
RNA Longo não Codificante , Neoplasias da Bexiga Urinária , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Fluorcarbonetos , Humanos , Hidrocarbonetos Bromados , RNA Longo não Codificante/genética , Neoplasias da Bexiga Urinária/genética
14.
Braz J Med Biol Res ; 54(12): e11459, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34730679

RESUMO

Reportedly, circular RNAs (circRNAs) are crucial regulators in cancer progression. Nonetheless, the molecular mechanism of circRNAs in hepatocellular carcinoma (HCC) has not been fully clarified. Gene expression omnibus (GEO) database was employed to screen out the differentially expressed circRNAs in HCC. qRT-PCR and western blot were executed to detect circ_0001806 expression, miR-193a-5p expression, and MMP16 mRNA and protein expressions in HCC. The effect of circ_0001806 on HCC was analyzed by the CCK-8 method and Transwell experiment. RIP assay, pull-down experiment, and dual-luciferase reporter gene experiment were applied to validate the targeting relationships among circ_0001806, miR-193a-5p, and MMP16. Circ_0001806 was up-modulated in HCC tissues and cell lines. Knockdown of circ_0001806 impeded the multiplication, migration, and invasion of HCC cells. Circ_0001806 could up-regulate MMP16 expression through repressing miR-193a-5p, thereby facilitating the malignant biological behaviors of HCC. Circ_0001806 promoted HCC progression by regulating miR-193a-5p/MMP16 axis.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Humanos , Neoplasias Hepáticas/genética , Metaloproteinase 16 da Matriz , MicroRNAs/genética , RNA Circular
15.
J Int Med Res ; 49(11): 3000605211053158, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34738477

RESUMO

OBJECTIVE: P-element Induced WImpy protein-like RNA-mediated gene silencing 2 (PIWIL2) is a reported oncogene strongly associated with tumorigenesis and cancer progression. However, the potential function of PIWIL2 in oral cancer is still largely unclear. METHODS: In this study, we investigated the clinical significance of PIWIL2 expression in human oral squamous cell carcinoma (OSCC) cell lines and tissues. We also examined its function in OSCC pathogenesis by knocking down PIWIL2 expression with short hairpin RNAs, followed by phenotypic experiments focused on cell migration, invasion, proliferation, and apoptosis rates. RESULTS: We found that PIWIL2 was overexpressed in OSCC cell lines and tissues and significantly correlated with the malignancy stage. Furthermore, knockdown of PIWIL2 in a human OSCC cell line Tca8113 induced cell cycle arrest and apoptosis. Silencing PIWIL2 expression also significantly suppressed the migration and invasion abilities of Tca8113 cells. CONCLUSIONS: Collectively, our results suggest a functional role of PIWIL2 in regulating OSCC pathogenesis. Our data imply that PIWIL2 could serve as a potential therapeutic target for OSCC treatment.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Apoptose , Proteínas Argonauta/genética , Proteínas Argonauta/metabolismo , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Humanos , Neoplasias Bucais/genética , RNA Interferente Pequeno/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço
16.
J Int Med Res ; 49(11): 3000605211051581, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34738482

RESUMO

OBJECTIVE: To investigate Krüppel-like factor 17 (KLF17) expression in normal and gastric cancer tissues and cell lines. METHODS: Levels of KLF17 mRNA and protein in GES-1 normal gastric mucosal cells, and NCI-N87, SGC-7901, BGC-823 and HGC-27 gastric cancer cells were analysed by quantitative polymerase chain reaction (qPCR) and western blot. Differences in KLF17 expression between gastric cancer and adjacent tissues were analysed by qPCR and immunohistochemistry. Invasion/migration effects of KLF17 overexpression in BGC-823 and HGC-27 cells were analysed by wound-healing and Transwell chamber assays. Changes in expression of KLF17 and epithelial-mesenchymal transition (EMT)-related genes (matrix metalloproteinase [MMP]-9, vimentin and E-cadherin) were analysed in BGC-823 and HGC-27 cells before and after transfection using qPCR and western blot. Transforming growth factor (TGF)-ß1, Smad family member (Smad)2/3 and phosphorylated-Smad2/3 levels in BGC-823 and HGC-27 cells were assessed by qPCR and western blot. RESULTS: KLF17 expression was lower in gastric cancer versus adjacent tissues, and in gastric cancer cell lines versus GES-1 normal gastric mucosal cells, and was positively correlated with degree of cancer-cell differentiation. Wound-healing and Transwell assays showed decreased migration and invasion ability of BGC-823 and HGC-27 cells transfected to overexpress KLF17. KLF17 overexpression was associated with decreased MMP-9 and vimentin in BGC-823 and HGC-27 cancer cells, and increased KLF17 and E-cadherin. KLF17 overexpression also resulted in decreased levels of TGF-ß1 and p-Smad2/3 in BGC-823 and HGC-27 cancer cells. CONCLUSION: KLF17 is poorly expressed in gastric cancer tissues and cell lines. KLF17 overexpression might inhibit EMT via the TGF-ß/Smad pathway, thereby reducing gastric cancer cell invasion and migration. Therefore, KLF17 may become a novel target for treating gastric cancer.


Assuntos
Transição Epitelial-Mesenquimal , Neoplasias Gástricas , Linhagem Celular Tumoral , Movimento Celular , Humanos , Neoplasias Gástricas/genética , Fatores de Transcrição , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta1/genética
17.
J Nanosci Nanotechnol ; 21(6): 3580-3587, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34739810

RESUMO

The study focused on the medicinal properties of citrus fruits and their ability to synthesize silver nanoparticles. As the resistance against the modern antibiotic agents is on increase, finding new and effective natural antibiotic agents is the need of the modern era. Similarly, bio-synthesis of nanoparticles is also being encouraged for eco-friendly reasons. Due to remarkable medicinal and industrial applications of silver nanoparticles (AgNPs), citrus fruit juice is used to reduce silver ions for the green synthesis of AgNPs. Phytochemical analysis revealed the presence of various constituents which impart antibacterial property to citrus fruits, analyzed against four pathogenic bacteria. Also, citrus fruit juice exhibits radical scavenging activity because of these constituents. Further, the AgNPs synthesized using citrus fruits were characterized using Ultra-Violet Visible (UV-VIS) spectroscopy, Fourier Transform Infrared (FTIR) spectroscopy and Transmission Electron Microscopy (TEM) to study the shape and size of the AgNPs. Anticancer activity of AgNPs was also evaluated against Colo-205 cell lines and found to inhibit 37.9% growth of cell lines at the concentration of 10 µg/ml. Hence, synthesized AgNPs can be used effectively against cancer cell lines in combination with other anti-cancer agents.


Assuntos
Antineoplásicos/farmacologia , Citrus , Nanopartículas Metálicas , Antibacterianos/farmacologia , Linhagem Celular Tumoral , Frutas , Química Verde , Humanos , Testes de Sensibilidade Microbiana , Extratos Vegetais/farmacologia , Prata/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier
18.
Chin Med J (Engl) ; 134(21): 2619-2628, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34748526

RESUMO

BACKGROUND: Microribose nucleic acids (miRNAs) are implicated in the progression of lung adenocarcinoma. MicroRNA-345-5p (miR-345-5p) is a recently identified anti-oncogene in some human cancers, but its functional role and possible molecular mechanism in lung adenocarcinoma remain unknown. This study aimed to identify the biological function and underlying mechanism of miR-345-5p in lung adenocarcinoma cells. METHODS: In this study, lung adenocarcinoma tissues and adjacent tissues were collected in the First Affiliated Hospital of Anhui Medical University between April 2016 and February 2017. The expression of miR-345-5p and ras homolog family member A (RhoA) in lung adenocarcinoma tissues and human lung adenocarcinoma cell lines (A549, H1650, PC-9, and H441) was detected by reverse transcription quantitative polymerase chain reaction analysis. Functional assays including colony formation, flow cytometry analysis, wound healing, and transwell assays were performed to assess the proliferation, apoptosis, migration, and invasion of lung adenocarcinoma cells. In addition, RNA pulldown and luciferase reporter assays were conducted to evaluate the relationship between miR-345-5p and RhoA. Difference between the two groups was analyzed with Student's t test, while that among multiple groups was analyzed with one-way analysis of variance. RESULTS: MiR-345-5p expression displayed lower level in lung adenocarcinoma tissues (0.241 ± 0.095 vs.1.000 ± 0.233, t = 19.247, P < 0.001) and cell lines (F = 56.992, P < 0.001) than control tissues and cells. Functional experiments demonstrated that upregulation of miR-345-5p inhibited the malignant phenotypes of lung adenocarcinoma cells via suppressing cell proliferation, migration, invasion, and facilitating cell apoptosis. Additionally, RhoA was verified to be the downstream target of miR-345-5p. Expression of RhoA was downregulated by overexpression of miR-345-5p in PC-9 (0.321 ± 0.047 vs. 1.000 ± 0.127, t = 8.536, P < 0.001) and H1650 (0.398 ± 0.054 vs. 1.000 ± 0.156, t = 4.429, P = 0.011) cells. Rescue assays revealed that overexpression of RhoA rescued the suppressive effects of miR-345-5p upregulation on proliferation, migration, and invasion of lung adenocarcinoma cells. Further, miR-345-5p was found to regulate the Rho/Rho-associated protein kinase (ROCK) signaling pathway by downregulation of RhoA in lung adenocarcinoma cells. CONCLUSIONS: MiR-345-5p plays a tumor suppressor role in lung adenocarcinoma cells by downregulating RhoA to inactivate the Rho/ROCK pathway.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , MicroRNAs , Adenocarcinoma de Pulmão/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , MicroRNAs/genética , Regulação para Cima/genética , Quinases Associadas a rho/genética , Proteína rhoA de Ligação ao GTP/genética
19.
Biomater Sci ; 9(22): 7392-7401, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34751685

RESUMO

Advances in the development of modern cancer immunotherapy and immune checkpoint inhibitors have dramatically changed the landscape of cancer treatment. However, most cancer patients are refractory to immune checkpoint inhibitors because of low lymphocytic tumor infiltration and PD-L1 expression. Evidence suggests that viral oncolysis and immune checkpoint inhibitors have a synergistic effect that can improve the response to immune checkpoint inhibitors. In this study, we developed bioengineered cell membrane nanovesicles (PD1-BCMNs) with programmed cell death protein 1 (PD-1) to harbor oncolytic adenovirus (OA) and achieve a combination of immune checkpoint blockade and oncolytic virotherapy in one particle for cancer treatment. PD1-BCMNs could specifically deliver OA to tumor tissue; the infectivity and replication ability of the OA was preserved in the presence of neutralizing antibodies in vitro and in vivo. Selective oncolytic effects with oncolytic adenovirus led to an up-regulated expression of PD-L1 in the tumor microenvironment, turning immunologically 'cold' tumors into immunologically 'hot' tumors, presenting more targets for further enhanced target delivery. Notably, PD1-BCMNs@OA could effectively activate tumor-infiltrating T cells and elicit a strong anti-tumor immune response. Thus, PD1-BCMNs@OA may provide a clinical basis for combining oncolytic virotherapy with checkpoint inhibitors, enhancing the oncolytic adenovirus targeted delivery and significantly enhancing T cell immune responses, resulting in a stronger antitumor immunity response.


Assuntos
Inibidores de Checkpoint Imunológico , Terapia Viral Oncolítica , Adenoviridae/genética , Linhagem Celular Tumoral , Humanos , Imunoterapia
20.
Anal Chim Acta ; 1186: 339115, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34756251

RESUMO

Isolation and characterization of circulating tumor cells (CTCs) found in blood samples of cancer patients have been considered as a reliable source for cancer prognosis and diagnosis. A new continuous microfluidic platform has been designed in this investigation for simultaneous capture and characterization of CTCs based on their deformability. The deformability-based chip (D-Chip) consists of two sections of separation and characterization where slanted weirs with a gap of 7 µm were considered. Although sometimes CTCs and leukocytes have the same size, the deformability differs in such a way that can be exploited for enrichment purposes. MCF7 and MDA-MB-231 cell lines were used for the initial evaluation of the D-Chip performance. In the separation section, cancer cells were isolated based on deformability differences with an efficiency of higher than 93% (∼average capturing capacity of 2085 out of 2200 cancer cells ml-1) and with significantly high purity (15-40 WBCs ml-1; ∼5 log depletion of WBCs). Cancer cells were categorized based on the deformability difference in the characterization section. Subsequently, 15 clinical blood samples from breast cancer patients were analyzed by the D-Chip. Suggest 'The chip detected CTCs in all patient samples, processed the blood sample at a high throughput of 5.3 ml/h, and properly categorized CTCs based on deformability differences. Further characterization showed that the highly deformable breast cancer CTCs in our patient samples also showed higher potential of metastasis in support of a broader correlation between deformability of CTCs and metastatic behavior.


Assuntos
Técnicas Analíticas Microfluídicas , Células Neoplásicas Circulantes , Linhagem Celular Tumoral , Separação Celular , Humanos , Microfluídica
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