NO-Donating NSAIDs, PPAR𝛿, and Cancer: Does PPAR𝛿 Contribute to Colon Carcinogenesis?

Table 1

The pros and cons for a role of PPAR𝛿 in cancer.

	Evidence	Reference
Pros
	PPAR𝛿 expression is enhanced in colon cancer cells	[43]
	PPAR𝛿 expression is repressed by the APC gene	[44]
	PPAR𝛿 expression increases as tumor progresses	[45]
	PPAR𝛿 genetic disruption decreases tumorigenicity of colorectal cancer cells	[46]
	PPAR𝛿 activation accelerates intestinal adenoma growth in Min mice	[47]
	𝑃𝑝𝑎𝑟𝑑^−/− HCT116 cells exhibit decreased ability to form xenograft tumors	[46]
	Dietary fish oil/pectin protects against radiation-enhanced colon cancer by upregulating apoptosis, in part,	[48]
	through PPAR𝛿 suppression
	PPAR𝛿 expression levels are correlated with advanced pathological tumor stage in tumor patients	[49]
	PPAR𝛿-targeted removal of a hub node of the angiogenic network markedly impairs angiogenesis	[49]
	and tumor growth in mice
	Inhibition of PPAR𝛿 function reduces growth of epithelial ovarian cancer	[50]
	Activation of PPAR𝛿 upregulates VEGF in colon cancer cells	[51]
	PPAR𝛿 activation stimulates the proliferation of human breast and prostate cancer cell lines	[52]
	PGE2 indirectly transactivates PPAR𝛿 promoting cell survival and intestinal adenoma formation	[53]
Cons
	PPAR𝛿-null Min mice exhibit increased predisposition to intestinal tumorigenesis	[54]
	PPAR𝛿-deficient mice show higher polyp formation	[55]
	PPAR𝛿 agonists do not increase cell growth in human cancer cell lines	[56]
	PPAR𝛿 is dispensable for polyp formation in the intestine and colon of Min mice	[36]
	RNA interference against Ppard promotes proliferation of HCT116 cells	[57]
	Lung tumorigenesis is attenuated in mice with disrupted Ppard	[58]
	PPAR𝛿 does not modify impaired mismatch repair-induced neoplasia	[59]
	PPAR𝛿 promotes differentiation, inhibiting cell proliferation in keratinocytes	[60]
	PPAR𝛿 ligands inhibit TNFα-induced expression of the vascular cell adhesion molecule-1 and	[61]
	E-selectin in HUVEC, preventing inflammation
	Inhibition of colon carcinogenesis by a PPAR𝛿 agonist in an azoxymethane mouse model	[62]
	PPAR𝛿 activators inhibit TNF𝛼-induced endothelial inflammation, in part by interfering with	[63]
	the NF-κB signaling pathway
	PPAR𝛿 activation by a PPAR𝛿 agonist produces no change in colon cancer cell growth	[52]
	PPAR𝛿 activation by GW0742 inhibits colon polyp multiplicity in 𝑃𝑝𝑎𝑟𝑑^+/+ mice,	[64]
	but not in 𝑃𝑝𝑎𝑟𝑑^−/− mice