Fig. 5: In vitro inhibition of PDK1 or PDK1 knockout increased osimertinib sensitivity and inhibited colony formation.
From: 3-Phosphoinositide-dependent kinase 1 drives acquired resistance to osimertinib
a NCI-H1975 and NCI-H1975-OsiR cells were treated with PDKi, BX 795, and dose-dependent inhibition of PDK1 and pPDK1 are shown; b osimertinib XTT was performed on NCI-H1975 and NCI-H1975-OsiR cells in the presence or absence of BX 795 and shows that BX795 renders NCI-H1975-OsiR sensitive to osimertinib; c osimertinib XTT with or without BX 795 on PDK1 knockout clone, NCI-H1975-OsiR-PDK1-/-; d osimertinib XTT on re-expressing PDK1 into PDK1 KO clone, NCI-H1975-OsiR-PDK1++/++ in presence or absence of BX 795. e Generation of CRISPR-cas9 mediated PDK1 knockout clone, NCI-H1975-OsiR-PDK1-/- and rescue of PDK1 in the KO clone by stably expressing the PDK1 plasmid to make NCI-H1975-OsiR-PDK1++/++ clones; f XTT assay shows the effect of PDK1 KO on osimertinib sensitivity; g XTT shows rescue of PDK1 expression in the PDK1 KO clone reverted the resistance to osimertinib. h Transient expression of PDK1 into NCI-H1975-parental cells and osimertinib XTT on transiently expressing PDK1 cells; i, j Colony formation assay shows osimertinib differential sensitivity among all clones. Data shown represent the mean ± SE of three independent experiments.
