Figure 5

Combination of E6201 with an inhibitor of PI3K signalling. Melanoma cells were treated with increasing concentrations of E6201 (3 nM to 3 μM) in combination with 1, 5, 10, 20 and 30 μM LY294002. Synergy with co-inhibition of MEK and PI3K was determined by calculation of a combination index at each concentration. A combination index value of 1 indicates additivity, values < 1 indicate synergism, and values > 1 indicate antagonism. All six of the melanoma cell lines studied showed synergy with the combination of E6201 and LY294002, particularly between an E6201 concentration of 10nM to 1 μM. Interestingly, the more resistant cell lines, UACC647 and UACC558, demonstrated decreasing CI, and hence increasing synergy, with increasing concentrations of E6201.