Fig. 5: Spontaneously BRAFi-resistant A375 VRPP3 cells with a Rac1 N92I mutation are also highly resilient to MEK1/2 genetic depletion and pharmacological inhibition.
From: A critical role of FAK signaling in Rac1-driven melanoma cell resistance to MAPK pathway inhibition
A VRPP3 cells with non-targeting shRNAs (VEC) and cells with MEK1 knockdown (MEK1 KD), MEK2 knockdown (MEK2 KD), or MEK1/2 double knockdown (MEK1/2 DKD) were grown in the presence of DMSO vehicle, 3 µM vemurafenib (VEM) or 3 µM vemurafenib plus 3 nM cobimetinib (VEM/COBI). Fold change cell growth was measured over time via resazurin assay. The MEK knockdown cell lines grew comparably to vector control in the presence of vemurafenib or vemurafenib/cobimetinib treatment. SDS-PAGE and immunoblotting of lysates from the cell lines input into the experiment (B), and from cells recovered at the end of the experiment (C) confirmed strong, stable knockdown of MEK1 and MEK2 in the respective cell lines.
