Dataset Information

Metformin and Probiotics in the Crosstalk between Colitis-Associated Colorectal Cancer and Diabetes in Mice.

ABSTRACT: The co-occurrence of colorectal cancer (CRC) and diabetes mellitus along with inflammation and dismicrobism has been frequently reported. Several studies shed light on the antioncogenic potential of metformin on colorectal carcinogenesis. This study aimed to demonstrate that metformin in association with probiotics acts in a synergic effect in breaking the crosstalk, thus inhibiting CRC progression, improving diabetes, and reducing inflammation. Ninety-six male Balb/c mice, 6-8 weeks old, were divided into 16 control and experimental groups to assess the effect of the different treatments and combinations at the clinical, histological, and molecular levels. Metformin and probiotics showed beneficial outcomes on CRC and diabetes, alone and most importantly in combination. Their effects were exerted by inhibiting the inflammatory process whereby a downregulation of IL-6 and TNF-? as well as oxidative stress were depicted. The characterization of the effects of probiotics and metformin on CRC and diabetes sheds light on the role of inflammation and microbiota in this crosstalk. Deciphering the downstream signaling pathways elicited by these compounds will help in developing new effective targeted treatment modalities.

SUBMITTER: Kattar SA

PROVIDER: S-EPMC7408863 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Metformin and Probiotics in the Crosstalk between Colitis-Associated Colorectal Cancer and Diabetes in Mice.

Kattar Sahar Al SA Jurjus Rosalyn R Pinon Aline A Leger David Yannick DY Jurjus Abdo A Boukarim Chawki C Diab-Assaf Mona M Liagre Bertrand B

Cancers 20200710 7

The co-occurrence of colorectal cancer (CRC) and diabetes mellitus along with inflammation and dismicrobism has been frequently reported. Several studies shed light on the antioncogenic potential of metformin on colorectal carcinogenesis. This study aimed to demonstrate that metformin in association with probiotics acts in a synergic effect in breaking the crosstalk, thus inhibiting CRC progression, improving diabetes, and reducing inflammation. Ninety-six male Balb/c mice, 6-8 weeks old, were d ...[more]

PMID: 32664279

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Project description:BackgroundThe tumor-promoting role of tumor microenvironment (TME) in colorectal cancer has been widely investigated in cancer biology. Cancer-associated fibroblasts (CAFs), as the main stromal component in TME, play an important role in promoting tumor progression and metastasis. Hence, we explored the crosstalk between CAFs and microenvironment in the pathogenesis of colorectal cancer in order to provide basis for precision therapy.MethodsWe integrated spatial transcriptomics (ST) and bulk-RNA sequencing datasets to explore the functions of CAFs in the microenvironment of CRC. In detail, single sample gene set enrichment analysis (ssGSEA), gene set variation analysis (GSVA), pseudotime analysis and cell proportion analysis were utilized to identify the cell types and functions of each cell cluster. Immunofluorescence and immunohistochemistry were applied to confirm the results based on bioinformatics analysis.ResultsWe profiled the tumor heterogeneity landscape and identified two distinct types of CAFs, which myo-cancer-associated fibroblasts (mCAFs) is associated with myofibroblast-like cells and inflammatory-cancer-associated fibroblasts (iCAFs) is related to immune inflammation. When we carried out functional analysis of two types of CAFs, we uncovered an extensive crosstalk between iCAFs and stromal components in TME to promote tumor progression and metastasis. Noticeable, some anti-tumor immune cells such as NK cells, monocytes were significantly reduced in iCAFs-enriched cluster. Then, ssGSEA analysis results showed that iCAFs were related to EMT, lipid metabolism and bile acid metabolism etc. Besides, when we explored the relationship of chemotherapy and microenvironment, we detected that iCAFs influenced immunosuppressive cells and lipid metabolism reprogramming in patient who underwent chemotherapy. Additionally, we identified the clinical role of iCAFs through a public database and confirmed it were related to poor prognosis.ConclusionsIn summary, we identified two types of CAFs using integrated data and explored their functional significance in TME. This in-depth understanding of CAFs in microenvironment may help us to elucidate its cancer-promoting functions and offer hints for therapeutic studies.

Dataset Information

Metformin and Probiotics in the Crosstalk between Colitis-Associated Colorectal Cancer and Diabetes in Mice.

Publications

Metformin and Probiotics in the Crosstalk between Colitis-Associated Colorectal Cancer and Diabetes in Mice.

Similar Datasets

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