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1.
Biochim Biophys Acta Mol Basis Dis ; 1866(1): 165554, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31513833

RESUMO

Activation of interferon (IFN)-I signaling in B cells contributes to the pathogenesis of systemic lupus erythematosus (SLE). Recent studies have shown that myeloid-derived suppressor cells (MDSCs) significantly expand in SLE patients and lupus-prone MRL/lpr mice and contribute to the pathogenesis of SLE. However, the role of SLE-derived MDSCs in regulating IFN-I signaling activation of B cells remains unknown. Here, we demonstrate that expansions of MDSCs, including granulocyte (G)-MDSCs and monocytic (M)-MDSCs, during the progression of SLE were correlated with the IFN-I signature of B cells. Interestingly, G-MDSCs from MRL/lpr mice, but not M-MDSCs, could significantly promote IFN-I signaling activation of B cells and contribute to the pathogenesis of SLE. Mechanistically, we identified that the long non-coding RNA NEAT1 was over-expressed in G-MDSCs from MRL/lpr mice and could induce the promotion of G-MDSCs on IFN-I signaling activation of B cells through B cell-activating factor (BAFF) secretion. Importantly, NEAT1 deficiency significantly attenuated the lupus symptoms in pristane-induced lupus mice. In addition, there was a positive correlation between NEAT1 and BAFF with the IFN signature in SLE patients. In conclusion, G-MDSCs may contribute to the IFN signature in SLE B cells through the NEAT1-BAFF axis, highlighting G-MDSCs as a potential therapeutic target to treat SLE.

2.
Nanoscale ; 11(44): 21030-21045, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31674617

RESUMO

As a new kind of porous material, zeolitic imidazolate frameworks (ZIF-8) are built from zinc ions and 2-methylimidazolate and possess unique merits including high porosity, good structural regularity and tunability, adjustable surface functionality and intrinsic pH induced biodegradability. These advantages endow ZIF-8 with multiple functionalities and stimuli-responsive controlled release of loaded payloads by endogenous or exogenous means. In this review, we will summarize the recent advancement of ZIF-8 as nanocarriers for the loading of various molecules including chemotherapeutic drugs, photosensitizers, photothermal agents, and proteins to fabricate multifunctional nanocomposites for synergistic cancer therapy. In addition, the challenges and future developments in this area will be highlighted.

3.
Biomed Pharmacother ; 121: 109280, 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31715373

RESUMO

Coronary microvascular dysfunction (CMD) is the pathological basis and pathogenesis of diabetic cardiomyopathy (DCM). Propylene glycol alginate sodium sulfate (PSS) as heparinoid drug has many biological activities. Here, a novel PSS-loaded nanoparticle (PSS-NP) was prepared to study its effect on the CMD of DCM. We used diabetes mellitus rat induced by STZ to establish the CMD model of DCM, and the study was detected by echocardiography, histological analysis, transmission electron microscopy, immunofluorescence staining, enzyme-linked immunosorbent assay, real time-PCR analysis, liquid-chip analysis, western blot analysis and so on. The experimental results suggested that PSS-NP could improve the survival state of rats, cardiac function, myocardial morphology and coronary microcirculation structure disorders, and increase the number of microvessels. In addition, we demonstrated that PSS-NP could alleviate the CMD by improving endothelial function, anticoagulation and antioxidative stress. The outcomes of this study provided new treatment thoughts for the therapy of coronary microcirculation dysfunction in DCM.

5.
Small ; : e1903895, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31747128

RESUMO

Glucose oxidase (GOx) can react with intracellular glucose and oxygen (O2 ) to produce hydrogen peroxide (H2 O2 ) and gluconic acid, which can cut off the nutrition source of cancer cells and consequently inhibit their proliferation. Therefore, GOx is recognised as an ideal endogenous oxido-reductase for cancer starvation therapy. This process can further regulate the tumor microenvironment by increasing the hypoxia and the acidity. Thus, GOx offers new possibilities for the elaborate design of multifunctional nanocomposites for tumor therapy. However, natural GOx is expensive to prepare and purify and exhibits immunogenicity, short in vivo half-life, and systemic toxicity. Furthermore, GOx is highly prone to degrade after exposure to biological conditions. These intrinsic shortcomings will undoubtedly limit its biomedical applications. Accordingly, some nanocarriers can be used to protect GOx from the surrounding environment, thus controlling or preserving the activity. A variety of nanocarriers including hollow mesoporous silica nanoparticles, metal-organic frameworks, organic polymers, and magnetic nanoparticles are summarized for the construction of GOx-based nanocomposites for multimodal synergistic cancer therapy. In addition, current challenges and promising developments in this area are highlighted.

6.
Adv Mater ; : e1905271, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31680346

RESUMO

The unique tumor microenvironment (TME) facilitates cancer proliferation and metastasis, and it is hard to cure cancer completely via monotherapy. Herein, a multifunctional cascade bioreactor based on hollow mesoporous Cu2 MoS4 (CMS) loaded with glucose oxidase (GOx) is constructed for synergetic cancer therapy by chemo-dynamic therapy (CDT)/starvation therapy/phototherapy/immunotherapy. The CMS harboring multivalent elements (Cu1+/2+ , Mo4+/6+ ) exhibit Fenton-like, glutathione (GSH) peroxidase-like and catalase-like activity. Once internalized into the tumor, CMS could generate ·OH for CDT via Fenton-like reaction and deplete overexpressed GSH in TME to alleviate antioxidant capability of the tumors. Moreover, under hypoxia TME, the catalase-like CMS could react with endogenous H2 O2 to generate O2 for activating the catalyzed oxidation of glucose by GOx for starvation therapy accompanied with the regeneration of H2 O2 . The regenerated H2 O2 can devote to Fenton-like reaction for realizing GOx-catalysis-enhanced CDT. Meanwhile, the CMS under 1064 nm laser irradiation shows remarkable tumor-killing ability by phototherapy due to its excellent photothermal conversion efficiency (η = 63.3%) and cytotoxic superoxide anion (·O2 - ) generation performance. More importantly, the PEGylated CMS@GOx-based synergistic therapy combined with checkpoint blockade therapy could elicit robust immune responses for both effectively ablating primary tumors and inhibiting cancer metastasis.

7.
Transbound Emerg Dis ; 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31738013

RESUMO

African swine fever (ASF) is a virulent infectious disease of pigs. As there is no effective vaccine and treatment method at present, it poses a great threat to the pig industry once it breaks out. In this paper, we used ASF outbreak data and the WorldClim database meteorological data, and selected the CfsSubset Evaluator-Best First feature selection method combined with the random forest algorithms to construct an African swine fever outbreak prediction model. Subsequently, we also established a test set for data other than modeling, and the accuracy ACC value range of the model on the independent test set was 76.02%-84.64%, which indicated that the modeling effect was better and the prediction accuracy was higher than previous estimates. In addition, logistic regression analysis was conducted on 12 features used for modeling and the ROC curves were drawn. The results showed that the bio14 features (precipitation of driest month), had the largest contribution to the outbreak of ASF, and it was speculated that the outbreak of the epidemic was significantly related to precipitation. Finally, we used this qualitative prediction model to build a global online prediction system for ASF outbreaks, in the hope that this study will help to decision-makers who can then take the relevant prevention and control measures in order to prevent the further spread of future epidemics of the disease.

8.
ACS Nano ; 13(11): 13144-13160, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31609581

RESUMO

Tumor cell metabolism and tumor blood vessel proliferation are distinct from normal cells. The resulting tumor microenvironment presents a characteristic of hypoxia, which greatly limits the generation of oxygen free radicals and affects the therapeutic effect of photodynamic therapy. Here, we developed an oxygen-independent free radical generated nanosystem (CuFeSe2-AIPH@BSA) with dual-peak absorption in both near-infrared (NIR) regions and utilized it for imaging-guided synergistic treatment. The special absorption provides the nanosystem with high photothermal conversion efficiency and favorably matched photoactivity in both I and II NIR biological windows. Upon NIR light irradiation, the generated heat could prompt AIPH release and decompose to produce oxygen-independent free radicals for killing cancer cells effectively. The contrastive research results show that the enhanced therapeutic efficacy of NIR-II over NIR-I is principally due to its deeper tissue penetration and higher maximum permission exposure that benefits from a longer wavelength. Hyperthermia effect and the production of toxic free radicals upon NIR-II laser illumination are extremely effective in triggering apoptosis and death of cancer cells in the tumor hypoxia microenvironment. The high biocompatibility and excellent anticancer efficiency of CuFeSe2-AIPH@BSA allow it to be an ideal oxygen-independent nanosystem for imaging-guided and NIR-II-mediated synergistic therapy via systemic administration.

9.
Braz J Infect Dis ; 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31634439

RESUMO

Host immunogenetic setting is involved in the regulation of human papillomavirus (HPV) infection and development of condyloma acuminatum (CA). We investigated the correlation of two common single nucleotide polymorphisms (SNPs) (-607C/A and -137G/C) of IL-18 with the susceptibility of CA in a large Chinese cohort. Out of 408 CA patients analyzed, 300 had HPV infection transmitted through sexual contact (SC) and 108 through non-sexual contact (NSC). In addition, 360 healthy volunteers were enrolled as controls. SNPs at positions -607C/A and -137G/C in IL-18 promoter were analyzed. Comparing CA patients to healthy controls, no dominant relevance was found between the IL-18 promoter -607 C/A or -137G/C polymorphisms and the CA disease either identified genotypically (p > 0.05) or by allelically (p > 0.05). However, the IL-18 promoter -137G/C polymorphism genotype and allele frequencies in the NSC CA group, but not between in the SC group, were significantly higher than in the controls. There was no dominant relevance between IL-18-607C/A polymorphism genotype and allele frequencies among SC, NSC CA patients, and controls. Our study demonstrates that polymorphism -137G/C in IL-18 promoter is significantly correlated with risk of CA in NSC patients.

10.
Molecules ; 24(19)2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31590214

RESUMO

The chemical compositions of ethanol extracts of propolis from China (EEP-C) and the United States (EEP-A) and their antifungal activity against Penicillium notatum were determined. The result showed that a total of 49 compounds were detected by UPLC-Q-TOF-MS, 30 of which were present in samples from two regions. The major compounds of EEP-C and EEP-A were similar, including pinocembrin, pinobanksin-3-O-acetate, galanin, chrysin, pinobanksin, and pinobanksin-methyl ether, and both of them showed antifungal activity against P. notatum with same minimum inhibitory concentration (MIC) value of 0.8 mg·mL-1. In the presence of propolis, the mycelial growth was inhibited, the hyphae became shriveled and wrinkled, the extracellular conductivities were increased, and the activities of succinate dehydrogenase (SDH) and malate dehydrogenase (MDH) were decreased. In addition, iTRAQ-based quantitative proteomic analysis of P. notatum in response to propolis revealed that a total of 341 proteins were differentially expressed, of which 88 (25.8%) were upregulated and 253 (74.2%) were downregulated. Meanwhile, the differentially expressed proteins (DEPs) involved in energy production and conversion, carbohydrate transport and metabolism, and the sterol biosynthetic pathway were identified. This study revealed that propolis could affect respiration, interfere with energy metabolism, and influence steroid biosynthesis to inhibit the growth of P. notatum.

11.
Acta Biomater ; 99: 412-425, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31494294

RESUMO

Metastasis and chemotherapy resistance are the leading causes of breast cancer mortality. Celecoxib (CXB), a selective cyclooxygenase-2 (COX-2) inhibitor, has antiangiogenetic activity and inhibitory effect on tumor metastasis, and can also enhance the sensitivity of chemotherapeutic drug doxorubicin (DOX) in breast cancer. To combine anticancer effects of DOX and CXB more efficiently, we designed a pH-sensitive nanotherapeutic system based on propylene glycol alginate sodium sulfate (PSS), a marine sulfated polysaccharide that possesses anti-platelet aggregation activity and has been used as a heparinoid drug in China. A facile one-pot nanoprecipitation method was used to prepare this nanotherapeutic system named as PSS@DC nanoparticles, in which DOX and CXB were complexed to form hydrophobic nanocores and PPS coated these nanocores through conjugation with DOX via a highly acid-labile benzoic-imine linker. PSS@DC nanoparticles showed distinct pH-sensitivity and significantly accelerated the release of DOX at the acidic pH mimicking the tumor microenvironment and endocytic-related organelles. Compared to single- and mixed-drug treatments, PSS@DC nanoparticles notably inhibited the growth of mouse breast cancer 4T1 cells with an IC50 of about 0.82 µg/mL DOX, and meanwhile reduced cell migration, invasion and adhesion abilities more efficiently. In 4T1 tumor-bearing mice, PSS@DC nanoparticles exhibited good tumor-targeting ability and markedly inhibited tumor growth with an inhibition rate of approximately 73.3%, and furthermore suppressed tumor metastasis through anti-angiogenesis. In summary, this nanotherapeutic system shows a great potential for the treatment of metastatic breast cancer by combining chemotherapy and COX-2 inhibitor. STATEMENT OF SIGNIFICANCE: A pH-sensitive nanotherapeutic system (PSS@DC nanoparticles) containing both chemotherapeutic drug doxorubicin (DOX) and COX-2 specific inhibitor celecoxib was designed based on a marine sulfated polysaccharide that possesses anti-platelet aggregation activity and has been used as a heparinoid drug in China. PSS@DC nanoparticles had distinct pH-sensitivity and could accelerate the release of DOX at the acidic pH values of tumor microenvironment and endocytic-related organelles. Both in vitro and in vivo, PSS@DC nanoparticles showed synergistic effects on the suppression of breast tumor growth and metastasis by combining chemotherapy and COX-2 inhibition.

12.
ACS Appl Mater Interfaces ; 11(40): 36347-36358, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31525886

RESUMO

Photodynamic therapy (PDT) has been introduced as a photochemical process for treatment by causing cancer cell death and necrosis, with higher accuracy and few side effects. However, the hydrophobicity of most photosensitizers and hypoxia at the tumor sites are two crucial problems to be solved to achieve a successful PDT. Herein, we designed and constructed a novel metal-organic framework-based drug delivery system (BSA-MnO2/Ce6@ZIF-8) with tumor microenvironment controllability. In our system, the hydrophobic photosensitizer chlorin e6 (Ce6) was one-pot incorporated into the matrix of zeolitic imidazolate framework 8 (ZIF-8) to form the Ce6@ZIF-8 compound, which can efficiently keep the Ce6 molecules isolated and avoid them self-aggregate, and the loading rate of Ce6 was high up to 28.3 wt %. The bovine serum albumin (BSA)-MnO2 nanoparticles (NPs) with catalase-like activity were loaded onto the surface of ZIF-8, having the capacity for self-sufficiency of O2 under the circumstance of H2O2 in acid solution, relieving hypoxia in cancer cells and thereby improving the PDT efficiency greatly when irradiated by low power density (230 mW/cm2) 650 nm light. Moreover, the MnO2 NPs react with H2O2 in acid solution to produce Mn2+, granting the system the qualification of a contrast agent for magnetic resonance imaging. Therefore, our nanoplatform would further contribute to the treatment of hypoxic tumors in clinical practice.

13.
Biomaterials ; 223: 119473, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31499255

RESUMO

Drug delivery systems (DDSs) have emerged to help delivering the required cargo into the region of the tumor, achieving the objectives of extenuating the potential damage to the body and improving the therapeutic effectiveness. Here, we developed a one-pot process for encapsulating the unstable and hydrophobic d-α-Tocopherol succinate (α-TOS) in zeolitic imidazolate framework-8 (ZIF-8) compounds (defined as α-TOS@ZIF-8) and subsequently coated with a hyaluronic acid (HA) shell to form the HA/α-TOS@ZIF-8 nanoplatform. Of particular note was when the concentration of α-TOS is l mg/mL, the loading rate was high up to 43.03 wt%. The study verified that HA shell, which could act as a smart "switch" and tumor-targeted "guider", had the capacity for extending blood circulation, enhancing the tumor-specific accumulation of DDS via CD44-mediated pathway. HA shell could be disintegrated by hyaluronidase (HAase) in the tumor microenvironment (TME) and the wrapped α-TOS@ZIF-8 exposed, thus leading to the decomposition of ZIF-8 in tumor acidic microenvironment to release the loaded α-TOS. Therefore, the HA/α-TOS@ZIF-8 nanoplatform has been achieved as a tumor-specific and on-demand drug delivery system, which improved the treatment efficiency.

14.
J Phys Condens Matter ; 31(46): 465002, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31425148

RESUMO

Photocatalytic water-splitting for hydrogen generation is a promising way to solve the energy crisis, yet the design of efficient photocatalysts is still a challenge. By utilization of first principles calculations, we predict the photocatalytic properties of monolayer boron phosphide (BP) based BP/XY2 (X = Mo, W; Y = S, Se) composites of different rotated configurations. Our results suggest that the BP/XY2 composites can be stably formed, and the narrowed bandgaps ensure these composites are suitable for absorbing visible light. The bandgaps and band edge positions are slightly affected by the rotation angles. The BP/MoS2, BP/MoSe2, and BP/WSe2 are type II heterostructures. Furthermore, the transferred charge from BP to XY2 layers leads to the formation of electric fields, which efficiently separate the photoinduced carriers. The band alignments of BP/MoS2, BP/MoS2, BP/MoSe2, and BP/WSe2 satisfy the requirements of overall water-splitting within the pH scope of 3.6-7.9, 6.8-7.9, 4.0-8.0, and 8.7-8.8. This work will provide valuable insight for designing efficient water-splitting photocatalysts.

15.
Front Immunol ; 10: 1824, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31428103

RESUMO

Macrophages play a critical role in the pathogenesis of endotoxin shock by producing excessive amounts of pro-inflammatory cytokines. A pan-caspase inhibitor, zVAD, can be used to induce necroptosis under certain stimuli. The role of zVAD in both regulating the survival and activation of macrophages, and the pathogenesis of endotoxin shock remains not entirely clear. Here, we found that treatment of mice with zVAD could significantly reduce mortality and alleviate disease after lipopolysaccharide (LPS) challenge. Notably, in LPS-challenged mice, treatment with zVAD could also reduce the percentage of peritoneal macrophages by promoting necroptosis and inhibiting pro-inflammatory responses in macrophages. In vitro studies showed that pretreatment with zVAD promoted LPS-induced nitric oxide-mediated necroptosis of bone marrow-derived macrophages (BMDMs), leading to reduced pro-inflammatory cytokine secretion. Interestingly, zVAD treatment promoted the accumulation of myeloid-derived suppressor cells (MDSCs) in a mouse model of endotoxin shock, and this process inhibited LPS-induced pro-inflammatory responses in macrophages. Based on these findings, we conclude that treatment with zVAD alleviates LPS-induced endotoxic shock by inducing macrophage necroptosis and promoting MDSC-mediated inhibition of macrophage activation. Thus, this study provides insights into the effects of zVAD treatment in inflammatory diseases, especially endotoxic shock.

17.
Genome ; 62(8): 563-569, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31158327

RESUMO

Heat shock transcription factors (Hsfs) are important regulators of biotic and abiotic stress responses in plants. Currently, the Hsf gene family is not well understood in cassava, an important tropical crop. In the present study, 32 MeHsf genes were identified from the cassava genome database, which were divided into three types based on functional domain and motif distribution analyses. Analysis of the differential expression of the genes belonging to the Hsf family in cassava was carried out based on published cassava transcriptome data from tissues/organs (leaf blade, leaf midvein, lateral buds, organized embryogenic structures, friable embryogenic callus, fibrous roots, storage roots, stem, petiole, shoot apical meristem, and root apical meristem) under abiotic stress (cold, drought) or biotic stress (mealybugs. cassava brown streak disease, cassava bacterial blight). The results show the expression diversity of cassava Hsfs genes in various tissues/organs. The transcript levels of MeHsfB3a, MeHsfA6a, MeHsfA2a, and MeHsfA9b were upregulated by abiotic and biotic stresses, such as cold, drought, cassava bacterial blight, cassava brown streak disease, and mealybugs, indicating their potential roles in mediating the response of cassava plants to environment stresses. Further interaction network and co-expression analyses suggests that Hsf genes may interact with Hsp70 family members to resist environmental stresses in cassava. These results provide valuable information for future studies of the functional characterization of the MeHsf gene family.

18.
Immunology ; 157(3): 257-267, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31120548

RESUMO

Asthma is a chronic inflammatory disease that involves a variety of cytokines and cells. Interleukin-16 (IL-16) is highly expressed during allergic airway inflammation and is involved in its development. However, its specific mechanism of action remains unclear. In the present study, we used an animal model of ovalbumin (OVA)-induced allergic asthma with mice harboring an IL-16 gene deletion to investigate the role of this cytokine in asthma, in addition to its underlying mechanism. Increased IL-16 expression was observed during OVA-induced asthma in C57BL/6J mice. However, when OVA was used to induce asthma in IL-16-/- mice, a diminished inflammatory reaction, decreased bronchoalveolar lavage fluid (BALF) eosinophil numbers, and the suppression of OVA-specific IgE levels in the serum and BALF were observed. The results also demonstrated decreased levels of T helper type 2 (Th2) and Th17 cytokines upon OVA-induced asthma in IL-16-/- mice. Hence, we confirmed that IL-16 enhances the lung allergic inflammatory response and suggest a mechanism possibly associated with the up-regulation of IgE and the promotion of Th2 and Th17 cytokine production. This work explored the mechanism underlying the regulation of IL-16 in asthma and provides a new target for the clinical treatment of asthma.

19.
Plant Dis ; 103(7): 1693-1702, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31106703

RESUMO

Companion cropping with wheat (Triticum aestivum L.) can enhance watermelon [Citrullus lanatus (Thunb.) Matsum. & Nakai] wilt disease resistance against Fusarium oxysporum f. sp. niveum. However, the mechanism of resistance induction remains unknown. In this study, the effects of microbial community dynamics and the interactions between wheat and watermelon plants, particularly the effect of wheat root exudates on watermelon resistance against F. oxysporum f. sp. niveum, were examined using a plant-soil feedback trial and plant tissue culture approach. The plant-soil feedback trial showed that treating watermelon with soil from wheat/watermelon companion cropping decreased watermelon wilt disease incidence and severity, increased lignin biosynthesis- and defense-related gene expression, and increased ß-1,3-glucanase activity in watermelon roots. Furthermore, soil microbes can contribute to increasing disease resistance in watermelon plants. Tissue culture experiments showed that both exogenous addition of wheat root exudates and companion cropping with wheat increased host defense gene expression, lignin and total phenols, and increased ß-1,3-glucanase activity in watermelon roots. In conclusion, both root exudates from wheat and the related soil microorganisms in a wheat/watermelon companion cropping system played critical roles in enhancing resistance to watermelon wilt disease induced by F. oxysporum f. sp. niveum.


Assuntos
Citrullus , Resistência à Doença , Fusarium , Triticum , Agricultura/métodos , Citrullus/crescimento & desenvolvimento , Citrullus/microbiologia , Resistência à Doença/efeitos dos fármacos , Resistência à Doença/fisiologia , Fusarium/fisiologia , Doenças das Plantas/prevenção & controle , Extratos Vegetais/farmacologia , Microbiologia do Solo , Triticum/química , Triticum/crescimento & desenvolvimento
20.
Mar Drugs ; 17(5)2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31035725

RESUMO

Melanoma is one of the most malignant and aggressive types of cancer worldwide. Fibroblast growth factor 2 (FGF2) is one of the critical regulators of melanoma angiogenesis and metastasis; thus, it might be an effective anti-cancer strategy to explore FGF2-targeting drug candidates from existing drugs. In this study, we evaluate the effect of the marine drug propylene glycol alginate sodium sulfate (PSS) on FGF2-mediated angiogenesis and invasion. The data shows that FGF2 selectively bound to PSS with high affinity. PSS inhibited FGF2-mediated angiogenesis in a rat aortic ring model and suppressed FGF2-mediated invasion, but not the migration of murine melanoma B16-F10 cells. The further mechanism study indicates that PSS decreased the expression of activated matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9), and also suppressed their activity. In addition, PSS was found to decrease the level of Vimentin in B16-F10 cells, which is known to participate in the epithelial-mesenchymal transition. Notably, PSS did not elicit any changes in cancer cell viability. Based on the results above, we conclude that PSS might be a potential drug to regulate the tumor microenvironment in order to facilitate the recovery of melanoma patients.


Assuntos
Alginatos/farmacologia , Fator 2 de Crescimento de Fibroblastos/metabolismo , Melanoma Experimental/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Alginatos/uso terapêutico , Animais , Aorta/efeitos dos fármacos , Organismos Aquáticos/química , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Embrião de Galinha , Membrana Corioalantoide , Avaliação Pré-Clínica de Medicamentos , Transição Epitelial-Mesenquimal , Humanos , Laminaria/química , Melanoma Experimental/irrigação sanguínea , Melanoma Experimental/patologia , Camundongos , Invasividade Neoplásica/patologia , Invasividade Neoplásica/prevenção & controle , Neovascularização Patológica/patologia , Neovascularização Fisiológica/efeitos dos fármacos , Técnicas de Cultura de Órgãos , Ratos , Neoplasias Cutâneas/irrigação sanguínea , Neoplasias Cutâneas/patologia , Microambiente Tumoral/efeitos dos fármacos
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