Table 1

Main COX-2 inhibitors tested in melanoma and their effect as possible therapeutic adjuvants

Study type	Cells type	Mutation	COX-2 inhibitor	Effects
In vitro⁵⁰	MTG2	NRAS^Q61R	Aspirin or celecoxib	Inhibits colony formation and migration
	MTG4	BRAF^V600E		Inhibits melanin synthesis
	MTG5	TP53^R213X and PDGFR-AD^846N
	A375	BRAF^V600E
	B16-F10
	YUSAC-2 (YU2)
In vivo				Delayed tumor development
				Inhibits proliferation of sensitive tumors
				Suppresses PGE₂ and activates AMPK
In vitro⁸⁴	B16-F10		Celecoxib	Dose dependent ROS-induced apoptosis
In vitro³⁹	KUL98-MELA	BRAF^V600E	Celecoxib	Reduced IDO-1 expression, may improve immunotherapy response
In vitro³¹	A375	BRAF^V600E	Celecoxib	PD-L1 and COX-2 down-regulation
	SK-MEL-2	NRAS^Q61R		Inhibits tumor growth, prevents cell proliferation, induces cell death
In vitro⁵⁸	SK-MEL-5	BRAF^V600E	Celecoxib	Reduced cellular proliferation and invasiveness
		NRAS^Q61		COX-2 overexpression is a negative prognostic factor
In vitro	WM35	BRAF^V600E	Selenocoxib-1-GSH (analog of celecoxib)	Inhibits cell proliferation
	WM115			Induces G0-G1 cell cycle arrest and apoptosis
	WM27.1
	A375M
	1205Lu
In vivo⁷⁵	UACC903			Inhibits PI3K/AKT signaling
	1205 Lu and UACC903
Case report⁸⁸	Nodular melanoma		Rofecoxib	Complete and long-lasting regression of skin metastasis