FIGURE 14.

UC-773587 and UC-857993 inhibit Ras signaling and growth of pancreatic and prostate cancer cells. UC-773587 (A) and UC-857993 (B) were tested for their ability to inhibit a 3-day cell growth of a panel of pancreatic and prostate cancer cell lines. Cells were grown in the presence of DMSO or indicated concentrations of UC-773587 or UC-857993 for 3 days and subsequently assayed for their growth by MTS as described under “Experimental Procedures.” C and D, DU-145 cells and Panc-1 cells were serum-starved for 24 h and pretreated with indicated concentrations of UC-773587 or UC-857993 for 16 h (DU-145-UC-773587), 2 h (DU-145-UC-857993), or 1 h (Panc-1-UC-773587 and UC-857993). Activation of phospho-ERK was measured by Western blot. Cell growth of DU-145 cells was measured in the presence of DMSO or indicated concentrations of UC-773587 (E) or UC-857993 (F) individually or in combination (G, left panel) over 72 h. Every 24 h of growth of the cells was assayed by MTS. G, right panel, combination treatment growth inhibition is represented as a bar graph at 72 h to assess additivity. Cell growth data were performed in triplicate or quadruplicate and represent the mean ± S.E. Data in A and B are plotted as relative growth on day 3 normalized to the DMSO control. Western blot data are representative of n = 3 experiments.