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1.
Oncol Lett ; 21(2): 143, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33552262

RESUMO

Fusobacterium nucleatum (Fn) is considered a promoting factor in colorectal cancer (CRC); however, only a few studies have investigated therapies against Fn. L-fucose is a natural monosaccharide that has prebiotic potential. The present study aimed to investigate the effect of L-fucose on the carcinogenic properties of Fn. The HCT116 and SW480 colon cancer cell lines were treated with Fn and Fn+L-fucose (Fnf), respectively. The Cell Counting Kit-8 (CCK-8), colony formation, Transwell migration and invasion and wound healing assays were performed to assess the proliferative, migratory and invasive abilities of the cells, respectively. Western blot was performed to detect the protein levels of jak/stat3 pathway components and EMT. The results of the CCK-8, colony formation, Transwell and wound healing assays demonstrated that treatment with Fn significantly enhanced the proliferative, migratory and invasive abilities of HCT116 and SW480 colon cancer cells. Notably, these effects were significantly reversed following addition of L-fucose. Furthermore, L-fucose inhibited the carcinogenic properties of Fn to activate the stat3 pathway and epithelial-to-mesenchymal transition. Taken together, the results of the present study suggest that L-fucose ameliorates the carcinogenic properties of Fn in vitro, and thus may serve as a novel therapeutic target for flora-related colon cancer.

2.
Int J Mol Med ; 47(1): 125-136, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33236145

RESUMO

Autophagy plays a dual role in the responses to the gut microflora. The present study aimed to examine the effects of Lactobacillus rhamnosus (L. rhamnosus) on Fusobacterium nucleatum (F. nucleatum)­induced intestinal dysfunction and to elucidate the underlying mechanisms, with particular focus on autophagy. Inflammatory models were established by treatment with L. rhamnosus following F. nucleatum intervention using cells or a mouse model of dextran sulfate sodium (DSS)­induced acute colitis. Autophagosomes were visualized by confocal microscopy following transfection with a tandem GFP­mCherry­LC3 construct and also by transmission electron microscopy. Autophagy­associated protein levels were examined by western blot analysis and immunohistochemistry. It was observed that F. nucleatum induced the production of pro­inflammatory cytokines in Caco­2 cells and aggravated DSS­induced acute colitis. The autophagic flux was impaired following infection with F. nucleatum. L. rhamnosus treatment attenuated the inflammation induced by F. nucleatum infection and effectively recovered the impaired autophagic flux. In addition, the production of pro­inflammatory cytokines induced by F. nucleatum was enhanced with autophagy inhibitors or the RNA interference of autophagy­related gene 16 like 1 (Atg16L1) in Caco­2 cells. Notably, this inhibition of autophagy weakened the effects of L. rhamnosus. Finally, the PI3K/AKT/mTOR pathway was found to be involved in this process. On the whole, the present study demonstrates that the mediation of autophagy by L. rhamnosus may be involved in the protective effects against F. nucleatum­related intestinal inflammation. Thus, L. rhamnosus treatment may prove to be a novel therapeutic strategy for F. nucleatum­realated gut disorders.


Assuntos
Autofagia , Colite/metabolismo , Infecções por Fusobacterium/metabolismo , Fusobacterium nucleatum/metabolismo , Lacticaseibacillus rhamnosus/metabolismo , Células CACO-2 , Colite/induzido quimicamente , Colite/patologia , Sulfato de Dextrana/toxicidade , Infecções por Fusobacterium/induzido quimicamente , Infecções por Fusobacterium/patologia , Humanos
3.
Cancer Lett ; 495: 165-179, 2020 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-32920199

RESUMO

By establishing the Fusobacterium nucleatum (F. nucleatum) infected-bone mesenchymal stem cells (BMSCs) transplantation model in APCMin/+ mice, we investigated the role of BMSCs in the development of intestinal tumors induced by F. nucleatum. ApcMin/++F. nucleatum + BMSCs mice showed increased susceptibility to intestinal tumors and accelerated tumor growth. BMSCs could also enhance tumor-initiating capability, invasive traits after F. nucleatum infection in vitro, and tumorigenicity in a nude murine model. Mechanistically, BMSCs were recruited to the submucosa, migrated to the mucosal layer, and might activate the canonical Wnt/ß-catenin/TGIF axis signaling. Further mechanistic results illustrated increased production of the Wnt3a protein was found in ApcMin/++F. nucleatum + BMSCs mice, and BMSCs were likely the major source of Wnt3a. Intriguingly, a deletion of Wnt3a via BMSC interference or antagonist analogs led to a significantly attenuated capacity of ApcMin/++F. nucleatum mice to generate intestinal tumors. The findings suggest that BMSCs have the potential to migrate and accelerate F. nucleatum-induced colorectal tumorigenesis by modulating Wnt3a secretion; knockdown of BMSC-derived Wnt3a or antagonist analogs could attenuate carcinogenesis. Thus, Wnt3a might be a potential pharmaceutical target for the prevention and treatment of F. nucleatum-related colorectal cancer.


Assuntos
Neoplasias Colorretais/terapia , Infecções por Fusobacterium/complicações , Fusobacterium nucleatum/patogenicidade , Células-Tronco Mesenquimais/citologia , Proteína Wnt3A/genética , Animais , Células CACO-2 , Linhagem Celular Tumoral , Neoplasias Colorretais/microbiologia , Feminino , Infecções por Fusobacterium/genética , Infecções por Fusobacterium/terapia , Técnicas de Silenciamento de Genes , Células HT29 , Humanos , Masculino , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Camundongos , Via de Sinalização Wnt , Proteína Wnt3A/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
4.
PLoS One ; 9(3): e90153, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24595218

RESUMO

BACKGROUND AND AIMS: Research has increasingly suggested that gut flora plays an important role in the development of post-infectious irritable bowel syndrome (PI-IBS). Studies of the curative effect of probiotics for IBS have usually been positive but not always. However, the differences of treatment effects and mechanisms among probiotic stains, or mixture of them, are not clear. In this study, we compared the effects of different probiotics (Befidobacterium, Lactobacillus, Streptococcus or mixture of the three) on intestinal sensation, barrier function and intestinal immunity in PI-IBS mouse model. METHODS: PI-IBS model was induced by Trichinella spiralis infection in mice. Different probiotics were administered to mice after 8 weeks infection. Visceral sensitivity was measured by scores of abdominal withdrawal reflex (AWR) and the threshold intensity of colorectal distention. Colonic smooth muscle contractile response was assessed by contraction of the longitudinal muscle strips. Plasma diamine oxidase (DAO) and d-lactate were determined by an enzymatic spectrophotometry. Expression of tight junction proteins and cytokines in ileum were measured by Western blotting. RESULTS: Compared to control mice, PI-IBS mice treated either alone with Befidobacterium or Lactobacillus (but not Streptococcus), or the mixture of the three exhibited not only decreased AWR score and contractile response, but also reduced plasma DAO and D-lactate. These probiotic treatments also suppressed the expression of proinflammatory cytokine IL-6 and IL-17 and promoted the expression of major tight junction proteins claudin-1 and occludin. The mixture of the three probiotic strains performed better than the individual in up-regulating these tight junction proteins and suppressing IL-17 expression. CONCLUSIONS: Bifidobacterium and Lactobacillus, but not Streptococcus, alleviated visceral hypersensitivity and recovered intestinal barrier function as well as inflammation in PI-IBS mouse model, which correlated with an increase of major tight junction proteins. In addition, Mixture of three species was indicated to be superior to a single one.


Assuntos
Bifidobacterium , Intestinos/fisiologia , Lactobacillus , Probióticos , Streptococcus , Animais , Western Blotting , Citocinas/metabolismo , Mucosa Intestinal/fisiologia , Intestinos/imunologia , Camundongos , Permeabilidade , Especificidade da Espécie
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