Figure 3. Treatment with PLX4032 and ATRA in combination increases PLX4032 sensitivity in A375R cells. (A) A375 and A375R cells were treated with the indicated concentrations of PLX4032 or PD98059 (10 μM), alone or in combination for 24 h, after which cell viability was measured via MTT assays. Points, mean of three experiments; bars, S.D.; **p<0.01. (B) A375 and A375R cells were treated with PLX4032 (1 μM) or PD98059 (10 μM), alone or in combination, for 24 h, then the cells were harvested and whole cell lysates were immunoblotted using relevant antibodies. (C) A375 and A375R cells with indicated concentrations of PLX4032 or ATRA (20 μM), alone or in combination, for 24 h, after which cell viability was measured via MTT assays. Points, mean of three experiments; bars, S.D.; **p<0.05. (D) A375 and A375R cells with PLX4032 (1 μM) or the indicated concentrations of ATRA, alone or in combination, for 24 h, then the cells were harvested and whole-cell lysates were immunoblotted using appropriate antibodies. (E-F) A375 and A375R cells were exposed to PLX4032 (1 μM) or ATRA (20 μM), alone or in combination, in soft agar matrix and incubated at 37°C in a 5% CO2 atmosphere for 14 days. Colonies from three separate experiments are illustrated. The average number of colonies was measured. Columns, mean of three experiments; bars, S.D.; **p<0.01.