Fig. 5.

Reduced FN render previously insensitive, 3D tumor aggregates susceptible to a broad range of drugs. a Viability curves of Scr and shFN cells treated with MTT in 2D show negligible differences for pharmacological inhibitors cisplatin, vemurafenib and vx-11e. b Schematic showing the timing of drug administration for cells embedded in 3D soft agar with treatment commencing after colony formation. A375-Scr cells are insensitive to inhibitors of the MAPK pathway, whereas A375 shFN2 cells show increased sensitivity to MAPK inhibition at dosages determined from the IC₅₀ curves. c Similar comparison of colonies formed from A375. S2-Scr cells show greater sensitivity to inhibitors of the MAPK pathway. Colonies of A375.S2 shFN2 cells were further reduced in number following treatment by all inhibitors. Significance was determined by student’s t- test, comparing within conditions to control where * indicates p <0.05, ** indicates p <0.01, *** indicates p <0.001, **** indicates a p <0.0001