Fig 6. Hypothetical schema of comparison of drug resistance effect in 2D and 3D environments due to cell-to-cell interaction.

The 2D cell culture environment and 3D cell culture environment reacted to rapamycin and BCG treatment, and there were strong differences. The mTOR signal pathway was more highly blocked by rapamycin in 2D than in 3D. The secretion of IL-6, IL-12, and IFN-γ, which are antitumor cytokines, due to BCG was also increased more in 2D than in 3D, resulting in an enhanced antitumor effect on bladder cancer cells. This indicates that our model confirms the secretion of E-cadherin and N-cadherin and shows the difference in drug resistance according to the difference in the intensity of cell-to-cell interaction. The results provide a rationale for evaluating drugs using the 3D cell culture environment.