Protective links between vitamin D, inflammatory bowel disease and colon cancer

Table 2 Vitamin D and mouse models of colitis-associated colon cancer

Strain	Model	Vitamin D metabolite/analog	Dose, route	Treatment window and duration	Serum vit D measure	Outcome	Ref.
Vitamin D Supplementation
A/J	AOM + DSS (3%), 7 d	Ro26-2198 (analog)	0.01 μg/kg per day, subcutaneous pump	1 wk prior to AOM	ND	Delayed onset of clinical colitis, decreased cellular proliferation and decreased dysplasia following AOM/DSS	[43]
CF1	AOM + DSS (2.5%) × 7 d	D3, 25(OH)D, 1,25(OH)2D3 and 1,25(OH)2D5	500 μg D3/kg diet , - 500 μg 25(OH)D/kg diet, 2.5 μg 1,25(OH)2D3/kg diet and 25 μg 1,25(OH)2D5/kg diet	1 wk prior to AOM + DSS treatment and maintained throughout study	ND	D3, 25(OH)D, and 1,25(OH)2D5 significantly decreased tumor incidence. 1,25(OH)2D3 induced significant weight loss compared to other treatments; not included in final analysis	[118]
C57BL/6	AOM + DSS (2%), 4 d × 3 cycles	D3	100, 400, 1000, 2500 or 5000 IU/kg diet, diet	2.5 wk prior to AOM + DSS treatment	25(OH)D	Vitamin D supplementation significantly decreased dysplasia in a dose dependent manner	[42]
Smad3-/-	Helicobacter bilis	D3	1000 IU or 5000 IU/kg diet, diet	1 wk prior to infection; maintain throughout study	25(OH)D	Higher vitamin D significantly decreased tumor incidence	[39]
Vitamin D Deficiency
Smad3-/-	Helicobacter bilis	NA	Vit D deficient diet	2 wk prior to infection; maintain throughout study	25(OH)D	No change in dysplasia score or tumor incidence	[39]
Other (VDR Knockout)
Vdr-/-	AOM + DSS (1.5%), 5 d × 3 cycles	NA	NA	NA	ND	Increased inflammation and tumor burdens; increased activation of EGFR and ErbB2 signaling	[145]

AOM: Azoxymethane; D₃: Vitamin D₃; DSS: Dextran sodium sulfate; EGFR: Epidermal growth factor receptor; ErbB2: Receptor tyrosine-protein kinase erbB-2; NA: Not applicable; ND: Not done; Vit: Vitamin.