Weight Loss and/or Sulindac Mitigate Obesity-associated Transcriptome, Microbiome, and Protumor Effects in a Murine Model of Colon Cancer.

Autor:	Bowers LW; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina., Glenny EM; Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina., Punjala A; School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina., Lanman NA; Center for Cancer Research, Purdue University, West Lafayette, Indiana.; Department of Comparative Pathobiology, Purdue University, West Lafayette, Indiana., Goldbaum A; Department of Nutrition Science, Purdue University, West Lafayette, Indiana., Himbert C; Department of Population Health Sciences, University of Utah, Salt Lake City, Utah., Montgomery SA; Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina., Yang P; Department of Palliative, Rehabilitation, and Integrative Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas., Roper J; Department of Medicine, Duke University, Durham, North Carolina., Ulrich CM; Department of Population Health Sciences, University of Utah, Salt Lake City, Utah., Dannenberg AJ; Department of Medicine (retired), Weill Cornell Medical College, New York, New York., Coleman MF; Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina., Hursting SD; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.; Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.; Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, North Carolina.
Jazyk:	angličtina
Zdroj:	Cancer prevention research (Philadelphia, Pa.) [Cancer Prev Res (Phila)] 2022 Aug 01; Vol. 15 (8), pp. 481-495.
DOI:	10.1158/1940-6207.CAPR-21-0531
Abstrakt:	Obesity is associated with an increased risk of colon cancer. Our current study examines whether weight loss and/or treatment with the NSAID sulindac suppresses the protumor effects of obesity in a mouse model of colon cancer. Azoxymethane-treated male FVB/N mice were fed a low-fat diet (LFD) or high-fat diet (HFD) for 15 weeks, then HFD mice were randomized to remain on HFD (obese) or switch to LFD [formerly obese (FOb-LFD)]. Within the control (LFD), obese, and FOb-LFD groups, half the mice started sulindac treatment (140 ppm in the diet). All mice were euthanized 7 weeks later. FOb-LFD mice had intermediate body weight levels, lower than obese but higher than control (P < 0.05). Sulindac did not affect body weight. Obese mice had greater tumor multiplicity and burden than all other groups (P < 0.05). Transcriptomic profiling indicated that weight loss and sulindac each modulate the expression of tumor genes related to invasion and may promote a more antitumor immune landscape. Furthermore, the fecal microbes Coprobacillus, Prevotella, and Akkermansia muciniphila were positively correlated with tumor multiplicity and reduced by sulindac in obese mice. Coprobacillus abundance was also decreased in FOb-LFD mice. In sum, weight loss and sulindac treatment, alone and in combination, reversed the effects of chronic obesity on colon tumor multiplicity and burden. Our findings suggest that an investigation regarding the effects of NSAID treatment on colon cancer risk and/or progression in obese individuals is warranted, particularly for those unable to achieve moderate weight loss. Prevention Relevance: Obesity is a colon cancer risk and/or progression factor, but the underlying mechanisms are incompletely understood. Herein we demonstrate that obesity enhances murine colon carcinogenesis and expression of numerous tumoral procancer and immunosuppressive pathways. Moreover, we establish that weight loss via LFD and/or the NSAID sulindac mitigate procancer effects of obesity. (©2022 American Association for Cancer Research.)
Databáze:	MEDLINE
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