(A) Western blot analysis of cetuximab plus AMG510 combinatorial
treatment in time course in C106, RW7213, SNU1411 and SW837 CRC cell lines.
RAS-GTP pull down assay is included, and Vinculin is used as loading control.
(B) Short-term proliferation assay of C106, RW7213, SNU1411 and SW837 treated
with increasing concentration of AMG510 with or without 50ug/mL cetuximab. First
data points of the combination curves represent the response to cetuximab alone.
Cells were treated for 120 hours with increasing concentration of AMG510 and
then ATP content was measured using CellTiterGlo. Data represents the average
and standard deviation of 3 biological replicates. The AMG510 single agent
curves used in this graph, are the same used in fig 1A. (C) Long-term drug screening proliferation assay of C106,
RW7213, SNU1411 and SW837 treated with increasing concentration of AMG510 with
or without 50μg/mL cetuximab. Cetuximab only treated cells are shown in
the first lower circles. Cells were treated for 9 to 13 days according to the
time when untreated controls reached confluence. (D) CellTox assay of C106,
RW7213, SNU1411 and SW837 treated with increasing concentration of AMG510 with
or without 50μg/mL cetuximab. Cetuximab only treated cells are shown as
the first red bar at 0μM AMG510. Cells were treated for 120 hours. Data
represents the average and standard deviation of 3 biological replicates.
Statistical significance was calculated using one-way ANOVA with
Bonferroni’s correction. Asterisks indicates *=p<0.05,
**=p<0.01, ***=p<0.001, ****=p<0.0001, n.s.= not
significant. (E) LIM1215 KRAS G12C Knock-In (KI) clones response to cetuximab;
LIM1215 parental cells were included as control. (F) LIM1215 KRAS G12C KI clones
response to AMG510 in short-term proliferation assay. Cells were treated for 120
hours with increasing concentration of AMG510 and then ATP content was measured
using CellTiterGlo. Data represents the average and standard deviation of 3
biological replicates. (G) LIM1215 KRAS G12C KI clones response to
AMG510+cetuximab in short-term proliferation assay. First data points of the
combination curves represent the response to cetuximab alone. Cells were treated
for 120 hours with increasing concentration of AMG510 and then ATP content was
measured using CellTiterGlo. Data represents the average and standard deviation
of 3 biological replicates. (H) HCA46-R Pmab cell line response to
AMG510+cetuximab in short-term proliferation assay. First data point of the
combination curve represents the response to cetuximab alone. Cells were treated
for 120 hours with increasing concentration of AMG510 and then ATP content was
measured using CellTiterGlo. Data represents the average and standard deviation
of 3 biological replicates. (I) Long-term drug screening proliferation assay of
HCA46-R Panitumumab treated with increasing concentration of AMG510 with or
without 50ug/mL cetuximab. Cetuximab only treated cells are shown in the first
lower circles. (J) CellTox assay of HCA46-R Pmab treated with increasing
concentration of AMG510 with or without 50ug/mL cetuximab. Cetuximab only
treated cells are shown as the first red bar at 0μM AMG510. Data
represents the average and standard deviation of 3 biological replicates.
Statistical significance was calculated using one-way ANOVA with
Bonferroni’s correction. Asterisks indicates *=p<0.05,
**=p<0.01, ***=p<0.001, ****=p<0.0001, n.s.= not
significant.