Hypercholesterolemia resulting in
atherosclerosis is associated with an increased risk of
ischemic heart disease and
colorectal cancer (CRC). However, the roles of apoliprotein (
Apo) E (
Apoe) and
low-density lipoprotein (
Ldl) receptor (Ldlr) in colorectal
carcinogenesis have not yet been investigated. In this study, we examined the susceptibility of
Apoe-deficient and Ldlr-deficient mice, which are genetic animal models of
atherosclerosis to
azoxymethane (AOM)/
dextran sodium sulfate (DSS)-induced colorectal
carcinogenesis. In Experiment 1, male
Apoe-deficient (n = 20) and wild type (WT) mice (C57BL/6J, n = 21) were treated with a single intraperitoneal (i.p.) injection of AOM (10 mg/kg
body weight) and then given 1.5% DSS in
drinking water for seven days. They were maintained up to week 20 and sacrificed for the histopathological examination of
colorectal tumors. The
mRNA expression of
cyclooxygenase (Cox)-2,
inducible nitric oxide synthase (Nos2),
tumor necrosis factor (Tnf)-α
interleukin (Il)-1β, and
Il-6 was assayed in the colorectal mucosa. In Experiment 2, male Ldlr-deficient (n = 14) and WT mice (C57BL/6J, n = 10) were given a single i.p. injection of AOM (10 mg/kg
body weight) and then given 2% DSS in
drinking water for seven days. They were sacrificed at week 20 to evaluate their colorectum histopathologically. In Experiment 1, the multiplicity of
CRCs was significantly higher in the
Apoe-deficient mice (2.75 ± 1.48) than in the WT mice (0.62 ± 0.67). The serum
lipoprotein levels in the
Apoe-deficient mice were also significantly higher than in the WT mice. In Experiment 2, the incidence (29%) and multiplicity (0.50 ± 0.94) of
CRCs in the Ldlr mice were significantly lower than in the WT mice (80% incidence and 3.10 ± 2.38 multiplicity). The
mRNA expression of two inducible
enzymes and certain pro-inflammatory
cytokines in the colorectum of each genotype was greater than in the respective WT mice. The values in the
Apoe-deficient mice were much greater than in the Ldlr mice. These findings suggest that
Apoe-deficient mice showed increased susceptibility to
inflammation-associated colorectal
carcinogenesis due to their high reactivity to inflammatory stimuli.