Abnormal
circadian clock has been identified as an independent
risk factor for
tumorigenesis, and is closely related to the occurrence and development of
tumor. As metabolic disorder is also one of the important characteristics of
tumorigenesis, therefore it is particularly important to investigate the regulatory relationship between
biological clock and
tumor metabolism. In this study, the effect of abnormal
circadian clock on
colon cancer growth was evaluated by
azoxymethane (AOM) /
dextran sodium sulfate (DSS) -induced
colitis-associated
carcinogenesis (CAC)
mice model. The result showed that abnormal
circadian clock aggravated anal swelling, redness, bloody and anorectal
prolapse in CAC
mice, and significantly increased the number and volume of CAC
polyps (P <0. 05 or P <0. 01), and reduced the intestinal length,
body weight,
survival rate of CAC
mice and the expression levels of inflammatory factors
IL-1β (
interleukin-1 beta) and TNFα (
tumor necrosis factor α) (P < 0. 05 or P < 0. 01), indicating that abnormal
biological clock promotes the occurrence and development of CAC. Further, non-target
metabonomics analysis of
serum samples from
mice was performed by
liquid chromatography-mass spectrometry (
LC-MS) . The result showed that compared with CAC
mice with normal
circadian rhythm, 27 differential metabolites were identified in CAC
mice with disrupted
circadian clock, and 9
metabolic pathways were enriched by KEGG (kyoto
encyclopedia of
genes and
genomes) database. These results suggest that abnormal
circadian clock can significantly change the relative abundance of some metabolites in
serum samples from CAC
mice, remodel
tumor metabolism, and result in the development of CAC in
mice. This study reveals the pivotal
role of
tumor metabolism in the abnormal
circadian clock promoting the
growth of CAC in
mice, providing a new experimental basis for the interaction between
circadian clock and metabolic
homeostasis in the occurrence and development of
colon cancer.