LY294002 potentiates the anti-cancer effect of oxaliplatin for gastric cancer via death receptor pathway

Figure 3 Effects of oxaliplatin, LY294002, or combination on recruitment of Fas-associated death domain protein, expression of Fas ligand and short form of cellular caspase-8/FLICE-inhibitory protein, and activation of caspase-8, Bid, and caspase-3. A-D: In MKN45 and AGS cells, oxaliplatin led to increased Fas ligand (FasL) expression, Fas-associated death domain protein (FADD) recruitment, caspase-8 and caspase-3 activation, and Bid cleavage (t-Bid formation). LY294002 significantly promoted these oxaliplatin-induced changes. Oxaliplatin reduced short form of cellular caspase-8/FLICE-inhibitory protein (c-FLIP_S) expression, while LY294002 enhanced this effect of oxaliplatin. Oxaliplatin and LY294002 did not modulate long form of cellular caspase-8/FLICE-inhibitory protein expression (data not shown). IP: Immunoprecipitation; WB: Western blotting.