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. Author manuscript; available in PMC: 2020 Sep 19.
Published in final edited form as: Cell Chem Biol. 2019 Jun 27;26(9):1240–1252.e11. doi: 10.1016/j.chembiol.2019.06.003

Figure 5. Foretinib kills NSCLC cells through a polypharmacology mechanism involving inhibition of MEK1/2, FER and AURKB.

Figure 5.

(A) Western blot of pERK (T202/Y204) after 1 hour treatment of H1155 cells with 0.1, 0.5 and 1 μM foretinib (FORE) or cabozantinib (CABO), 0.1 μM of PF-04217903 (PF-METi) or 0.1 μM of motesanib (MOTE - VEGFRi). Blots are representative of three independent experiments.

(B) Western blot of pH3 (S10) after 6 hours treatment of H1155 cells with 0.05, 0.25 and 0.5 μM of foretinib (FORE) and 0.05 μM of barasertib (AURKBi). Blots are representative of three independent experiments.

(C) Cell cycle analysis of H1155 cells after 6 hours of treatment with foretinib (FORE) and cabozantinib (CABO) at indicated concentrations, n = 3, Data are represented as mean + SD.

(D) Immunopreciptation of tyrosine phosphorylated FER in H1155 cells after 3 hours treatment with 1 μM each of foretinib (FORE), saracatinib (SARA – SRCi), GSK1838705A (GSK - FERi), cabozantinib (CABO) or DMSO control. TCL: total cell lysate. Blots are representative of three independent experiments.

(E) H1155 cell viability upon treatment with GSK1838705A (2.5 μM), barasertib (50 nM) and trametinib (35 nM) alone or in indicated combinations. Cell viability was determined by CellTiter-Glo assay after 72 hours of treatment and normalized to DMSO (first white bar), n = 3, Data are represented as mean ± SD. *** indicates p value < 0.001 as determined using Student’s t-test.

(F) RNA interference of FER and AURKB in combination with trametinib (35 mM) in H1155 cells. Cell viability was determined after 72 hours of treatment with DMSO or trametinib by trypan blue-based cell counting, n = 3, Data are represented as mean ± SD. Blots are representative of three independent experiments. * and *** indicate p values of < 0.05 and < 0.001, respectively, as determined using Student’s t-test.