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Figure 4.
Figure 4: WZ4002 inhibits EGFR phosphorylation and induces
significant tumour regression in murine models of EGFR T790M.
a, Two doses separated by 16 h of WZ4002 (2.5 mg kg^-1 or 25 mg
kg^-1) or vehicle were administered to EGFR delE746_A750/T790M
or L858R/T790M mice with MRI-confirmed tumours. The mice were
killed, the lungs isolated, grossly dissected and subjected to
cell lysis. Cell extracts were immunoblotted to detect the
indicated proteins. b, Immunohistochemical analyses of tumours
from EGFR delE746_A750/T790M mice from a using indicated
antibodies. Scale bar, 50 μm. c, Quantification of TUNEL- and
Ki67-positive cells from tumour nodules (n = 4) from vehicle-
and WZ4002-treated mice. The means and standard deviations are
plotted. *, P < 0.05. d, MRI images of vehicle- or
WZ4002-treated mice at baseline (0 weeks: 0w) and after 2 weeks
(2w) of treatment. e, Quantification of the relative tumour
volume from MRI images from vehicle-treated mice
(E746_A750/T790M (n = 3); L858R/T790M (n = 4)), and
WZ4002-treated L858R/T790M (n = 3) and E746_A750/T790M (n = 3)
mice. The means and standard deviations are plotted. f, Tumours
from vehicle- and WZ4002-treated mice stained with haematoxylin
and eosin. Low-power view (inset) demonstrates near-complete
resolution of tumours in the WZ4002-treated mice. Scale bar, 100
μm.
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