Validation of a 3D culture model for toxicity studies in malignant and non-cancerous cells

Abstract: Cancer is a widespread and commonly fatal disease in constant need of new treatments. Traditionally, new pharmaceuticals have been tested in 2D models. This is not ideal, as 2D environments do not reflect the in vivo milieu of the cells. Instead, it has been increasingly suggested to implement 3D models, which are thought to be more predictive of in vivo responses to treatment. It has been shown that cancerous cells are less sensitive to anti-cancer drugs when cultured in 3D. Thus, this study aimed to compare the effect of 2D and 3D environments on the potency of the MEK inhibitor trametinib in human cancerous A549 and non-cancerous LL47 cells. The 3D model used was an electrospun poly-caprolactone membrane, on which the cells were seeded and then treated with varying trametinib concentrations. The 2D model was a traditional cell culture plate. The study also investigated the mechanism of trametinib. It was shown that trametinib affects the amount of p-ERK, in line with data published by others. No statistically significant difference in potency could be shown between the models. However, after optimisation the 3D model itself was shown to be working and giving reproducible results, suggesting further use in preclinical studies.