Abstract
Background and AimCalcium has been proposed as a mediator of the chemoprevention of colorectal cancer (CRC), but the comprehensive mechanism underlying this preventive effect is not yet clear. Hence, we conducted this study to evaluate the possible roles and mechanisms of calcium-mediated prevention of CRC induced by 1,2-dimethylhydrazine (DMH) in mice.MethodsFor gene expression analysis, 6 non-tumor colorectal tissues of mice from the DMH + Calcium group and 3 samples each from the DMH and control groups were hybridized on a 4×44 K Agilent whole genome oligo microarray, and selected genes were validated by real-time polymerase chain reaction (PCR). Functional analysis of the microarray data was performed using KEGG and Gene Ontology (GO) analyses. Hub genes were identified using Pathway Studio software.ResultsThe tumor incidence rates in the DMH and DMH + Calcium groups were 90% and 40%, respectively. Microarray gene expression analysis showed that S100a9, Defa20, Mmp10, Mmp7, Ptgs2, and Ang2 were among the most downregulated genes, whereas Per3, Tef, Rnf152, and Prdx6 were significantly upregulated in the DMH + Calcium group compared with the DMH group. Functional analysis showed that the Wnt, cell cycle, and arachidonic acid pathways were significantly downregulated in the DMH + Calcium group, and that the GO terms related to cell differentiation, cell cycle, proliferation, cell death, adhesion, and cell migration were significantly affected. Forkhead box M1 (FoxM1) and nuclear factor kappa-B (NF-κB) were considered as potent hub genes.ConclusionIn the DMH-induced CRC mouse model, comprehensive mechanisms were involved with complex gene expression alterations encompassing many altered pathways and GO terms. However, how calcium regulates these events remains to be studied.
Highlights
The current incidence of colorectal cancer (CRC) is high, and its prognosis remains poor [1]; it is important to devise strategies to prevent the development of CRC
A recent study suggested that calcium could abrogate hyperplasia in the distal colon by inhibiting a calcium channel receptor, i.e., transient receptor potential channel, subfamily V, member 6 (TRPV6) [16]. These findings indicate that calcium could reduce the risk of CRC through a variety of mechanisms, but the specific and comprehensive mechanism is yet not clear
Because we think that the controversial effectiveness of high calcium diet on the prevention of CRC may be partially due to the small dose of calcium in previous studies, so we decided to use higher calcium content to test the exact preventive effect of CRC and the mice’s tolerance
Summary
The current incidence of colorectal cancer (CRC) is high, and its prognosis remains poor [1]; it is important to devise strategies to prevent the development of CRC. A recent systemic review revealed that calcium may be more attractive in the prevention of CRC compared with aspirin and screening [8]. Pooled findings of 10 cohort studies revealed a reverse relationship between calcium intake and CRC risk [9], but this relationship was not confirmed by a randomized controlled clinical trial [10]. The effectiveness of calcium on the prevention of CRC remains controversial [12]. Calcium has been proposed as a mediator of the chemoprevention of colorectal cancer (CRC), but the comprehensive mechanism underlying this preventive effect is not yet clear. We conducted this study to evaluate the possible roles and mechanisms of calcium-mediated prevention of CRC induced by 1,2-dimethylhydrazine (DMH) in mice
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