1. Pharmacologic inhibition of eIF5A hypusination sensitizes KRas-driven tumor cells to MEK and KRas inhibition.
Pharmacologic inhibition of eIF5A hypusination sensitizes KRas-driven tumor cells to MEK and KRas inhibition. A, The 779E cells were treated with the indicated concentration of GC7 and/or AZD6244 for 7 days and cell colonies stained with crystal violet. Bar graph (left) shows stained colony area as measured by ImageJ relative to vehicle control. Western blot analysis (right) was performed from treated cells for the indicated proteins. B, HPAF-II cells were treated with GC7 (20 μmol/L) and AZD6244 (1 μmol/L) and subjected to the colony growth assay and Western blotting as in A. C, The 779E cells were treated with GC7 or AZD6244 alone or in combination with the indicated drug concentrations and allowed to grow for 7 days. Cell colony area was assessed as in A. D, Nude mice subcutaneously implanted with 779E cells were treated with vehicle, GC7, AZD6244 or GC7, and AZD6244 for 8 days and tumor size was measured every other day. E, The relative body weights of mice treated with drugs as in D. F, Lysates from tumors in D were Western blotted for the indicated proteins. G, H1792 cells were treated with DFMO (0.5 mmol/L) or K-RasG12C compound 12 alone (0.5 μmol/L) or in combination and allowed to grow for 4 days. Cell colony area was assessed as in A. Western blot of drug-treated cells is shown in Supplementary Fig. S5E. *, P < 0.05; **, P < 0.01, Student t test.
Ken Fujimura et al. Cancer Res 2018;78:
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