Table 4. Comparison between COX-2-dependant and COX-2-independent effect of NSAIDs.

COX-2, cyclooxygenase-2; NSAIDs, nonsteroidal anti-inflammatory drugs; PGE, prostaglandins E; Wnt, signaling pathway; NF-kB, nuclear factor Kappa light chain enhancer of activated B cells; P53, cellular tumor antigen; NOS-2, nitric oxide synthase 2; P21, potent cyclin dependant kinase inhibitor; STAT 3, signaling transducer and activator of transcription; TNF, tumor necrosis factor; IL, interleukin, AMPK, adenosine monophosphate protein kinase; PCNA, proliferating cell nuclear antigen; p65, transcription factor of p 65

COX-dependent effect	COX-independent effect
Catalyze the synthesis of prostaglandins and PGE2, which stimulate proliferation of cancer cells, inhibit apoptosis, act as pro-inflammatory and immunosuppressive and stimulate tumor angiogenesis with dose 81-325 mg per day	-wnt, β-catenin, NF-κB, p53, toll-like receptor 4, NOS-2, and caspases for (aspirin). -p21, p53, Wnt, NF-κB, STAT3, TNF-α, IL-1β, IL-4, AMPK, PCNA, cyclin D1, β-catenin, inducible NOS, COX-2, and p65 (for sulindac with dose 300 mg per day)