(A) Relative short-term viability (CTG) of PA-TU-8902 cells stably
expressing control and SHOC2 targeting shRNAs via growth in low-attachment
assays in combination with trametinib (10 nM) treatment for 6 days. Immunoblot
of SHOC2 expression below. Error bars represent average relative CTG
proliferation readings of three biological replicates (n = 3) ± SEM.
(B) Relative viability (CTG three-dimensional) of SHOC2 KO PA-TU-8902
single-cell clones (SCCs) and parental grown in 100% Matrigel domes in
combination with trametinib (10 nM) treatment for 7 days. Immunoblot of SHOC2
expression below. Bars represent the average of three independent replicates
± SD.
(C) Tumor volume (mm3) growth kinetics of PA-TU-8902 sgRNA
intergenic control cells subcutaneously injected (3 × 106) in
SHO-immunocompromised mice treated with or without trametinib.
(D) Tumor volume growth kinetics of PA-TU-8902 SHOC2 KO cells
subcutaneously injected (3 × 106) in SHO mice treated with or
without trametinib.
(E) Tumor volume growth kinetics of PA-TU-8902 MAPK1 KO cells
subcutaneously injected (3 × 106) in SHO mice treated with or
without trametinib.
(F) Combined tumor volume growth kinetics of PA-TU-8902. sgRNA
intergenic control, SHOC2 KO, and MAPK1 KO tumors. Statistical significance ***p
≤ 0.001 and ****p ≤ 0.0001, and error bars represent ±
SEM.